Novel isoindole derivatives

ABSTRACT

This invention relates to compounds represented by the general formula [I] 
                 
 
     wherein, R represents an azido group, etc., R 1  and R 2  are the same or different and represent hydrogen atoms, etc., R 3  and R 4  are the same or different and represent hydrogen atoms, etc., X 1  represents an oxygen atom, etc., X 2  represents an oxygen atom, etc., Y represents an oxygen atom, etc., and Z represents a condensed aryl group, etc., or a pharmaceutically acceptable salt thereof, preparation processes thereof, and an agent for treating diabetes, a prophylactic agent for chronic complications of diabetes or a drug against obesity, containing, as an effective ingredient, the compound or the pharmaceutically acceptable salt thereof.

TECHNICAL FIELD

[0001] Blood glucose levels in normal subjects are maintained atconstant levels by insulin action. Diabetes mellitus is characterized bychronic hyperglycemia due to lost in the control of blood glucose level.

[0002] Basically, diabetes therapy aims to correct hyperglycemia, thatis by decreasing blood glucose into normal loevel. Accordingly, theimportance of therapeutic control on postprandial hyperglycemia withoutaffecting fasting glucose level is getting a great deal of attention.

[0003] Currently, besides insulin injection, major drugs for diabetestreatment are classified into three: First group of drugs is calledinsulin secretagogues, and is represented by sulfonylureas. These drugsdirectly induce insulin secretion from pancreas. Insulin then reducesblood glucose level. Drugs from the second group are called insulinsensitizers, which were launched recently. These drugs do not directlystimulate insulin release but enhance glucose uptake in the peripheraltissues. The third group of drugs is called α-glucosidase inhibitors,which are able to prevent from rapid increase in postprandial glucose.These drug's action is to suppress the transient rise in glucose leveloccurring during meal by delaying digestion and absorption of dietarycarbohydrate.

[0004] On the other hand, it is known that glucagon-like peptide-1(hereinafter, referred to as GLP-1) is a hormone secreted from L-cells,which are endocrine cells existing in the intestinal epithelium of smallintestine. GLP-1 lowers blood glucose level by inducing insulinsecretion from β-cells existing in the pancreatic islet of Langerhans(Eur. J. Clin. Invest, volume 22, page 154, 1992). Importantly, it isreported that the effect of GLP-1 on insulin secretion is dependent onglucose, that is GLP-1 induces insulin secretion only when blood glucoselevel is high and does not induce it during normoglycemia (Lancet,volume 2, page 1300, 1987). GLP-1 also enhances insulin biosynthesis(Endocrinology, volume 130, page 159, 1992) and acceleratesproliferation of β-cells (Diabetologia, volume 42, page 856, 1999).Therefore GLP-1 is not only stimulating insulin secretion but also is avery important hormone for the maintenance of pancreatic β-cells.

[0005] The efficacy of GLP-1 has been confirmed in patients with Type-IIdiabetes. The administration and maintaining high blood level of GLP-1significantly reduces hyperglycemia (Diabetologia, volume 36, page 741,1994 or ibid., volume 39, page 1546, 1996).

[0006] In addition, GLP-1 induces glucose utilization in peripheraltissues (Endocrinology, volume 135, page 2070, 1994 or Diabetologia,volume 37, page 1163, 1994). Intracerebroventricular injection of GLP-1induces feeding behavior (Digestion, volume 54, page 360, 1993). It isalso reported that GLP-1 reduced gastrointestinal motility (Dig. Dis.Sci., volume 43, page 1113, 1998).

[0007] Compounds closest to the compounds of the present invention instructure are described in U.S. Pat. No. 4,717,414 (hereinafter,referred to as Reference A) and J. Chem. Soc., Perkin Trans. 1, page1547, 1979 (hereinafter, referred to as Reference B).

[0008] The compounds of Reference A have an imidazoisoindole-dioneskeleton having an oxo group at the imidazo part condensing to theisoindole skeleton.

[0009] However, although the imidazoisoindole-dione skeleton is commonto the compounds of the invention and the compounds of Reference A, thecompounds of the invention have a functional group such as, for example,an aryl group at the substituent part at the 9-position on the skeletonand in that point are utterly different from the compounds of ReferenceA having a substituted alkyl group (R⁴C(Z)R⁵) such as, specifically forexample, a nitromethyl group or a 1-nitro-1-ethylmethyl group, instructure. Further, the use in Reference A is herbicides and is utterlydifferent from the invention in industrially applicable fields. Further,the preparation process in Reference A utilizes nucleophilic reaction ofalkyl carbon anions, etc. onto dihydroimidazoisoindole-dione, etc., andis utterly different from the preparation process of the inventionutilizing cyclization reaction.

[0010] Reference B discloses a compound having an oxazoloisoindole-dioneskeleton which has an oxo group at the oxazolo part condensing to theisoindole skeleton.

[0011] However, Reference B mainly discloses novel preparation processesof isoindolobenzazepine derivatives, and merely discloses that, in thereaction step, only one compound having an oxazoloisoindole-dioneskeleton is formed as a reaction by-product. The oxazoloisoindole-dioneskeleton is common to the compounds of the invention and the compound ofReference B, but the compounds of the invention having a functionalgroup such as, for example, an aryl group at the substituent part at the9-position on the skeleton and in that point are utterly different fromthe compound of Reference B which is Compounds (11) having anα-bromobenzyl group as the substituent, in structure.

[0012] Further, Japanese Laid-open Patent Publication (Tokuhyo-hei) No.507388/1994 (hereinafter, referred to as Reference C) and U.S. Pat. No.3,507,863 (hereinafter, referred to as Reference D) disclose tricyclicheterocycles wherein a 6-membered ring, a 5-membered ring and a5-membered ring are condensed.

[0013] Reference C discloses compounds having an oxazoloisoindoleskeleton or an imidazoisoindole skeleton wherein the oxazolo part or theimidazo part is condensed to the isoindole skeleton, respectively.

[0014] However, although the oxazoloisoindole skeleton or theimidazoisoindole skeleton are common to the compounds of the inventionand the compounds of Reference C, the compounds of the invention have afunctional group such as, for example, an oxo group or a thioxo group atthe the oxazolo part or the imidazo part condensed to the isoindoleskeleton and in that point are utterly different from the compounds ofReference C not having the oxo group or the like, in structure. Further,the use in Reference C is antiviral drugs and is the same in theindustrially applicable field, but is an use having no relation to theuse in the invention.

[0015] Reference D discloses compounds having an oxazoloisoindoleskeleton, an imidazoisoindole skeleton or a thiazoloisoindole skeletonwherein the oxazolo part, the imidazo part or the thiazolo part iscondensed to the isoindole skeleton, respectively.

[0016] However, although the oxazoloisoindole skeleton, theimidazoisoindole skeleton and the thiazoloisoindole skeleton are commonto the compounds of the invention and the compounds of Reference D, thecompounds of the invention have a functional group such as, for example,an oxo group or a thioxo group at the the oxazolo part, the imidazo partor the thiazolo part condensed to the isoindole skeleton and in thatpoint are utterly different from the compounds of Reference D not havingthe oxo group or the like, in structure. Further, the use in Reference Dis antiinflammatories or anticonvulsants and the same in theindustrially applicable field, but is an use having no relation to theuse in the invention.

[0017] As background art disclosing an invention having relation to theuse in the present invention, there can be mentioned U.S. Pat. No.3,928,597 (hereinafter, referred to as Reference E). Reference Ediscloses an invention of a method of treating hyperglycemia comprisingorally or parenterally administering a 2,3-dihydroimidazoisoindololcompound wherein a lower alkyl group is substituted at the imidazo partcondensed to the isoindole skeleton, and an imidazolylphenyl phenylketone compound.

[0018] However, although the imidazoisoindolone skeleton is common tothe compounds of the invention and the compounds of Reference E, thecompounds of the invention have a functional group such as, for example,an oxo group or a thioxo group at the imidazo part condensed to theisoindole skeleton and in that point are utterly different from thecompounds of Reference E not having the oxo group or the like, instructure. Moreover, the invention of Reference E is a use inventionwhich was attained by administering both of the2,3-dihydroimidazoisoindolol compound and the imidazolylphenyl phenylketone compound, each showing no antihyperglycemia effect solely, and isbased on interaction between the two kinds of compounds, as described inColumn 4 lines 39 to 45 of the specification, and is essentiallydifferent from the present invention in the subject of invention.

[0019] At present, drugs such as sulfonylureas, insulin sensitizers andα-glucosidase inhibitors are often used as anti-diabetic drugs. However,these drugs do not have satisfactory profiles. Indeed, sulfonylureas aredifficult to use for correction of postprandial hyperglycemia due toslow onset and long duration of action. Moreover, sulfonylureas causefasting hypoglycemia, which sometimes leads to fatal damage. Insulinsensitizers have side effects such as liver toxicity and edema.Therefore careful prescription of these drugs is necessary. As forα-glucosidase inhibitors, side effects such as flatulence and diarrheacome in to problema.

[0020] Therefore, it is necessary to develop much useful and saferanti-diabetic drugs which are able to regulate glucose level in a bloodglucose-dependent manner.

DISCLOSURE OF INVENTION

[0021] The present inventors have made intense researches for creatingdrugs for treating diabetes, capable of controlling blood glucose levelsdepending on the blood glucose levels, prophylactic agents for chroniccomplications of diabetes, or drugs against obesity, found that thecompounds of the general formula [I] attain high in vivo GLP-1concentration in the blood, and completed the invention.

[0022] This invention relates to isoindole derivatives, processes forpreparation thereof and uses thereof, and these inventions are notdisclosed in literatures and novel.

[0023] Description is made on definitions of various symbols and termsdescribed in the specification. Hereinafter, the terms “atom” and“group” are often omitted when being omitted is believed to be apparent,and for example, the term “(a) phenyl group(s)” is often abbreviatedmerely as “phenyl”, and “(a) hydrogen atom(s)” is often abbreviatedmerely as “hydrogen”.

[0024] As aryl groups, aryl groups having 6 to 15 carbon atoms arepreferred, and for example, naphthyl, phenyl, etc. are mentioned, andamong them phenyl, etc. are for example preferred.

[0025] As mono- to tricyclic C₇-C₁₅ aromatic carbocyclic groups,aromatic groups having 7 to 15 carbon atoms and having 1 to 3 cyclicgroups are preferred, and there can for example be mentionedacenaphthylenyl, adamantyl, anthryl, indenyl, norbornyl, phenanthryl,etc. and preferred among them are for example anthryl, phenanthryl, etc.

[0026] As 5- or 6-membered heterocyclic groups, there can for example bementioned isoxazolyl, isothiazolyl, imidazolyl, oxazolyl, oxadiazolyl,thiazolyl, thiadiazolyl, thienyl, triazinyl, triazolyl, pyridyl,pyrazinyl, pyrimidinyl, pyridazinyl, pyrazolyl, pyrrolyl, pyranyl,furyl, furazanyl, imidazolidinyl, imidazolinyl, tetrahydrofuranyl,pyrazolidinyl, pyrazolinyl, piperazinyl, piperidinyl, pyrrolidinyl,pyrrolinyl, morpholino, etc. (hereinafter. “isoxazolyl . . . morpholino”is referred to as a series of groups A), and preferred among them arefor example thienyl. tetrahydrofuranyl, pyridyl, pyrazinyl, pyrimidinyl,furyl, morpholino, etc.

[0027] As mono- to tricyclic aromatic heterocyclic groups having per onering 1 to 5 hetero atoms selected from the group consisting of nitrogenatoms, oxygen atoms and sulfur atoms, there can for example be mentionedacridinyl, isoquinolyl, isoindolyl, indazolyl, indolyl, indolizinyl,ethylenedioxyphenyl, carbazolyl, quinazolinyl, quinoxalinyl,quinolidinyl, quinolyl, cumaronyl, chromenyl, phenanthridinyl,phenanthrolinyl, dibenzofuranyl, dibenzothiophenyl, cinnolinyl,thionaphthenyl, naphthyridinyl, phenazinyl, phenoxazinyl,phenothiazinyl, phthalazinyl, pteridinyl, purinyl, benzimidazolyl,benzoxazolyl, benzothiazolyl, benzotriazolyl, benzofuranyl,methylenedioxyphenyl, etc. (hereinafter, “acridinyl . . . ,methylenedioxyphenyl” is referred to as a series of groups B), andpreferred among them are for example ethylenedioxyphenyl,dibenzofuranyl, dibenzothiophenyl, methylenedioxyphenyl, etc.

[0028] Halogen atoms mean fluorine, chlorine, bromine and iodine, andpreferred among them are fluorine, chlorine and iodine, and furtherpreferred among them are fluorine and chlorine.

[0029] As cyclic saturated C₃-C₉ aliphatic groups, cyclic alkyl groupshaving 3 to 9 carbon atoms, etc. are preferred, and among them cyclicalkyl groups having 3 to 6 carbon atoms, etc. are preferred.

[0030] As the cyclic alkyl groups, there can for example be mentionedcyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl,cyclooctyl, cyclononyl, etc., and preferred among them are for examplecyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, etc.

[0031] As cyclic unsaturated C₃-C₉ aliphatic groups, cyclic alkenylgroups having 3 to 9 carbon atoms, etc. are preferred, and among themcyclic alkenyl groups having 3 to 6 carbon atoms, etc. are preferred.

[0032] As the cyclic alkenyl groups, there can for example be mentionedcyclopropenyl, cyclobutenyl, cyclopentenyl, cyclohexenyl, cycloheptenyl,cyclooctenyl, cyclononenyl, etc., and preferred among them are forexample cyclopropenyl, cyclobutenyl, cyclopentenyl, cyclohexenyl, etc.

[0033] As aralkyl groups, aralkyl groups having 7 to 15 carbon atoms arepreferred, and there can specifically be mentioned for example benzyl,α-methylbenzyl,. phenethyl, 3-phenylpropyl, 1-naphthylmethyl,2-naphthylmethyl, α-methyl(1-naphthyl)methyl,α-methyl(2-naphthyl)methyl, α-ethyl(1-naphthyl)methyl,α-ethyl(2-naphthyl)-methyl, diphenylmethyl, etc., and in particularpreferred among them are benzyl, 1-naphthylmethyl, 2-naphthylmethyl,α-methylbenzyl, phenethyl, etc.

[0034] N-aralkylamino groups mean groups wherein an amino group issubstituted with the above-mentioned aralkyl group, and there canspecifically be mentioned for example N-benzylamino,N-(α-methylbenzyl)amino, N-phenethylamino, N-(3-phenylpropyl)-amino,N-(1-naphthylmethyl)amino, N-(2-naphthylmethyl)amino,N-[α-methyl(1-naphthyl)methyl]amino,N-[α-methyl(2-naphthyl)methyl]amino, N-[α-ethyl(1-naphthyl)methyl]amino,N-[α-ethyl(2-naphthyl)methyl]amino, diphenylmethylamino,N-(dinaphthylmethyl)amino, etc., and preferred among them areN-benzylamino, N-(α-methylbenzyl)amino, N-phenethylamino, etc.

[0035] N,N-di-aralkylamino groups mean groups wherein an amino group isdisubstituted with the above-mentioned aralkyl groups, and there can forexample be mentioned N,N-dibenzylamino, N,N-di(α-methylbenzyl)amino,N,N-diphenethylamino, N,N-di(3-phenylpropyl)amino,N,N-di(1-naphthylmethyl)amino, N,N-di(2-naphthyl-methyl)amino,N,N-di[α-methyl(1-naphthyl)methyl]amino,N,N-di[α-methyl(2-naphthyl)methyl]amino,N-benzyl-N-(α-methylbenzyl)amino, N-benzyl-N-phenethyl-amino,N-benzyl-N-(3-phenylpropyl)amino, etc., and preferred among them areN,N-dibenzylamino, N,N-di(α-methylbenzyl)amino, N,N-diphenethylamino,etc.

[0036] Aralkyloxy groups mean groups wherein an oxygen atom issubstituted with the above-mentioned aralkyl group, and there can forexample be mentioned benzyloxy, α-methylbenzyloxy, phenethyloxy,3-phenylpropoxy, 1-naphthylmethoxy, 2-naphthylmethoxy,α-methyl(1-naphthyl)methoxy, α-methyl(2-naphthyl)methoxy,α-ethyl(1-naphthyl)methoxy, α-ethyl(2-naphthyl)methoxy, diphenylmethoxy,dinaphthylmethoxy, etc., and preferred among them are benzyloxy,α-methyl-benzyloxy, phenethyloxy etc.

[0037] Aralkylcarbonyl groups mean groups wherein a carbonyl group issubstituted with the above-mentioned aralkyl group, and there can forexample be mentioned benzylcarbonyl, α-methylbenzylcarbonyl,phenethylcarbonyl, 3-phenylpropyl-carbonyl, 1-naphthylmethylcarbonyl,2-naphthylmethylcarbonyl, α-methyl(1-naphthyl)methylcarbonyl,α-methyl(2-naphthyl)methylcarbonyl, α-ethyl(1-naphthyl)methylcarbonyl,α-ethyl(2-naphthyl)methylcarbonyl, diphenylmethyl-carbonyl,dinaphthylmethylcarbonyl, etc., and preferred among them arebenzylcarbonyl, α-methylbenzylcarbonyl, phenethylcarbonyl, etc.

[0038] N-aralkylcarbamoyl groups mean groups wherein a carbamoyl groupis substituted with the above-mentioned aralkyl group, and there can forexample be mentioned N-benzylcarbamoyl, N-(α-methylbenzyl)carbamoyl,N-phenethylcarbamoyl, N-(3-phenylpropyl)carbamoyl,N-(1-naphthylmethyl)carbamoyl, N-(2-naphthylmethyl)-carbamoyl,N-(α-methyl(1-naphthyl)methyl)carbamoyl,N-(α-methyl(2-naphthyl)-methyl)carbamoyl,N-(α-ethyl(1-naphthyl)methyl)carbamoyl,N-(α-ethyl(2-naphthyl)methyl)carbamoyl, N-(diphenylmethyl)carbamoyl,N-(dinaphthyl-methyl)-carbamoyl, etc., and preferred among them areN-benzylcarbamoyl, N-(α-methylbenzyl)carbamoyl, N-phenethylcarbamoyl,etc.

[0039] N-arylamino groups mean groups wherein an amino group issubstituted with the above-mentioned aryl group, and there can forexample be mentioned N-phenylamino, N-(1-naphthyl)amino,N-(2-naphthyl)amino, etc., and preferred among them are N-phenylamino,etc.

[0040] N,N-diarylamino groups mean groups wherein an amino group isdisubstituted with the above-mentioned aryl groups, and there can forexample be mentioned N,N-diphenylammino, N,N-di(1-naphthyl)amino,N,N-di(2-naphthyl)amino, N-phenyl-N-(1-naphthyl)amino,N-phenyl-N-(2-naphthyl)amino, N-(1-naphthyl)-N-(2-naphthyl)-amino, etc.,and preferred among them are N,N-diphenylammino,N,N-di(1-naphthyl)amino, N,N-di(2-naphthyl)amino, etc.

[0041] Aryloxy groups mean groups wherein an oxygen atom is substitutedwith the above-mentioned aryl group, and there can for example bementioned phenoxy, naphthyloxy. etc., and preferred among them arephenoxy, etc.

[0042] Arylsulfonyl groups mean groups wherein a sulfonyl group issubstituted with the above-mentioned aryl group, and there can forexample be mentioned phenylsulfonyl, naphthylsulfonyl, etc., andpreferred among them are phenylsulfonyl, etc.

[0043] Arylsulfonyloxy groups mean groups wherein an sulfonyloxy groupis substituted with the above-mentioned aryl group, and there can forexample be mentioned phenylsulfonyloxy, naphthylsulfonyloxy, etc., andpreferred among them are phenylsulfonyloxy, etc.

[0044] N-arylsulfonylamino groups mean groups wherein an amino group isN-substituted with the above-mentioned arylsulfonyl group, and there canfor example be mentioned N-phenylsulfonylamino,N-(1-naphthylsulfonyl)amino, N-(2-naphthylsulfonyl)amino, etc., andpreferred among them are N-phenylsulfonylamino,N-(2-naphthylsulfonyl)-amino, etc.

[0045] As N-arylsulfonylamino C₁-C₁₀ alkylamino groups, groups whereinan amino group is N-substituted with an alkyl group having 1 to 10carbon atoms, having the above-mentioned arylsulfonylamino group arepreferred, and there can for example be mentionedN-phenylsulfonylaminomethylamino, N-(1-phenylsulfonylaminoethyl)-amino,N-(2-phenylsulfonylaminoethyl)amino, N-naphthylsulfonylaminomethylamino,N-(1-naphthylsulfonylaminoethyl)amino,N-(2-naphthylsulfonylaminoethyl)amino, etc., and preferred among themare N-phenylsulfonylaminomethylamino,N-(2-phenylsulfonylaminoethyl)amino, etc.

[0046] As N-arylsulfonylamino C₁-C₁₀ alkylcarbamoyl groups, groupswherein a carbamoyl group is N-substituted with an alkyl group having 1to 10 carbon atoms, having the above-mentioned arylsulfonylamino groupare preferred, and there can for example be mentionedN-phenylsulfonylaminomethylcarbamoyl,N-(1-phenylsulfonyl-aminoethyl)carbamoyl,N-(2-phenylsulfonylaminoethyl)carbamoyl,N-naphthyl-sulfonylaminomethylcarbamoyl,N-(1-naphthylsulfonylaminoethyl)-carbamoyl,N-(2-naphthylsulfonylaminoethyl)carbamoyl, etc., and preferred amongthem are N-phenylsulfonylaminomethylcarbamoyl,N-(2-phenylsulfonylaminoethyl)carbamoyl,N-(2-naphthylsulfonylaminoethyl)carbamoyl, etc.

[0047] As N-arylsulfonylamino C₁-C₁₀ alkoxylcarbonyl groups, groupswherein an alkoxycarbonyl group having 1 to 6 carbon atoms issubstituted with the above-mentioned N-arylsulfonylamino group arepreferred, and there can for example be mentionedN-phenylsulfonylaminomethoxycarbonyl,N-naphthylsulfonylamino-methoxycarbonyl,1-(N-phenylsulfonylamino)ethoxycarbonyl,2-(N-phenylsulfonyl-amino)ethoxycarbonyl, etc., and preferred among themare N-phenylsulfonyl-aminomethoxycarbonyl,N-naphthylsulfonylaminomethoxycarbonyl, etc.

[0048] Arylsulfamoyl groups mean groups wherein a sulfamoyl group issubstituted with the above-mentioned aryl group, and there can forexample be mentioned phenylsulfamoyl, naphthylsulfamoyl, etc., andpreferred among them are phenylsulfamoyl, etc.

[0049] Arylsulfamoyloxy groups mean groups wherein a sulfamoyloxy groupis substituted with the above-mentioned aryl group, and there can forexample be mentioned phenylsulfamoyloxy, naphthylsulfamoyloxy, etc., andpreferred among them are phenylsulfamoyloxy, etc.

[0050] As N-arylsulfamoyl C₁-C₁₀ alkylcarbamoyl groups, groups whereinan alkylcarbamoyl group having 1 to 10 carbon atoms is substituted withthe above-mentioned arylsulfamoyl group are preferred, and there can forexample be mentioned phenylsulfamoylmethylcarbamoyl,N-naphthylsulfamoylmethylcarbamoyl, etc., and preferred among them areN-naphthylsulfamoylmethylcarbamoyl, etc.

[0051] As arylsulfamoyl C₁-C₆ alkoxycarbonyl groups, groups wherein analkoxylcarbonyl group having 1 to 6 carbon atoms is substituted with theabove-mentioned arylsulfamoyl group are preferred, and there can forexample be mentioned phenylsulfamoylmethoxycarbonyl,naphthylsulfamoylmethoxycarbonyl, etc., and preferred among them arephenylsulfamoylmethoxycarbonyl, etc.

[0052] N-arylcarbamoyl groups mean groups wherein a carbamoyl group isN-substituted with the above-mentioned aryl group, and there can forexample be mentioned phenylcarbamoyl, naphthylcarbamoyl, and preferredamong them are phenylcarbamoyl, etc.

[0053] As C₂-C₆ alkanoyl groups, groups wherein a carbonyl group issubstituted with an alkyl group having 1 to 5 carbon atoms arepreferred, and there can for example be mentioned acetyl, propionyl,butyryl, isobutyryl, valeryl, isovaleryl, pivaloyl, pentanoyl, etc., andpreferred among them are acetyl, propionyl, pivaloyl, etc.

[0054] N—C₂-C₆ alkanoylamino groups mean groups wherein an amino groupis substituted with the above-mentioned C₂-C₆ alkanoyl group, and therecan for example be mentioned N-acetylamino, N-propionylamino,N-butyrylamino, N-isobutyrylamino, N-valerylamino, N-isovalerylamino,N-pivaloylamino, N-pentanoylamino, etc., and preferred among them areN-acetylamino, N-propionylamino, N-pivaloylamino, etc. N,N-di-C₂-C₆alkanoylamino groups mean groups wherein an amino group is disubstitutedwith the above-mentioned C₂-C₆ alkanoyl groups, and there can forexample be mentioned N,N-diacetylamino, N,N-dipropionylamino,N,N-dibutyrylamino, N,N-diisobutyrylamino, N,N-divalerylamino,N,N-diisovalerylamino, N,N-dipivaloylamino, N,N-dipentanoylamino,N-actyl-N-propionylamino, N-actyl-N-butyrylamino,N-actyl-N-pivaloylamino, etc., and preferred among them areN,N-diacetylamino, N,N-dipropionylamino, N,N-dibutyrylamino,N,N-dipivaloylamino, etc.

[0055] Aroyl groups mean groups wherein a carbonyl group is substitutedwith the above-mentioned aryl group, and there can for example bementioned benzoyl, naphthylcarbonyl, etc., and preferred among them arebenzoyl, etc.

[0056] Aroxy groups mean groups wherein an oxygen atom is substitutedwith the above-mentioned aroyl group, and there can for example bementioned benzoyloxy, naphthylcarbonyloxy, etc., and preferred amongthem are benzoyloxy, etc.

[0057] N-aroylamino groups mean groups wherein an amino group issubstituted with the above-mentioned aroyl group, and there can forexample be mentioned N-benzoylamino, N-naphthylcarbonylamino, etc., andpreferred among them are N-benzoylamino, etc.

[0058] As N-aroyl C₁-C₁₀ alkylamino groups, groups wherein an aminogroup is N-substituted with an alkyl group having 1 to 10 carbon atoms,having the above-mentioned aroyl group, are preferred, and there can forexample be mentioned N-benzoylmethylamino, N-(1-benzoylethyl)amino,N-(2-benzoylethyl)amino, N-naphthylcarbonylamino,N-(1-naphthylcarbonylethyl)amino, N-(2-naphthylcarbonyl-ethyl)amino,etc., and preferred among them are N-benzoylmethylamino,N-(2-benzoylethyl)amino, etc.

[0059] N-aroyl C₁-C₁₀ alkylcarbamoyl groups mean groups wherein acarbamoyl group is substituted with the above-mentioned N-aroyl C₁-C₁₀alkyl group, and there can for example be mentionedN-benzoylmethylcarbamoyl, N-(1-benzoylethyl)carbamoyl,N-(2-benzoylethyl)carbamoyl, N-naphthylmethylcarbonylcarbamoyl,N-(1-naphthyl-carbonylethyl)carbamoyl,N-(2-naphthylcarbonylethyl)carbamoyl, etc., and preferred among them areN-benzoylmethylcarbamoyl, N-(2-benzoylethyl)carbamoyl, etc.

[0060] N-(N-aroylamino) C₁-C₁₀ alkylcarbamoyl groups mean groups whereina carbamoyl group is substituted with the above-mentioned N-aroylaminoC₁-C₁₀ alkyl group, and there can for example be mentionedN-(N-benzoylaminomethyl)carbamoyl, N-(1-(N-benzoylamino)ethyl)carbamoyl,N-(2-(N-benzoyl)aminoethyl)carbamoyl,N-(N-naphthylcarbonylaminomethyl)carbamoyl,N-(1-(N-naphthylcarbonylamino)ethyl)-carbamoyl,N-(2-(N-naphthylcarbonylamino)ethyl)carbamoyl, etc., and preferred amongthem are N-(N-benzoylaminomethyl)carbamoyl,N-(2-(N-benzoylamino)ethyl)-carbamoyl, etc.

[0061] N-aroylamino C₁-C₁₀ alkoxycarbonyl groups mean groups wherein anoxycarbonyl group is substituted with the above-mentioned N-aroylaminoC₁-C₁₀ alkyl group, and there can for example be mentionedN-benzoylaminomethoxycarbonyl, 1-(N-benzoylamino)ethoxycarbonyl,2-(N-benzoylamino)ethoxycarbonyl,N-naphthyl-carbonylaminomethoxycarbonyl,1-(N-naphthylcarbonylamino)ethoxycarbonyl,2-(N-naphthylcarbonylamino)ethoxycarbonyl, etc., and preferred amongthem are N-benzoylaminomethoxycarbonyl,2-(N-benzoylamino)ethoxycarbonyl, etc.

[0062] As N—C₁-C₆ alkylamino groups, groups wherein an amino group isN-substituted with an alkyl group having 1 to 6 carbon atoms arepreferred, and there can for example be mentioned N-methylamino,N-ethylamino, N-propylamino, N-isopropylamino, N-butylamino,N-isobutylamino, N-sec-butylamino, N-tert-butylamino, N-pentylamino,N-neopentylamino, N-hexylamino, N-isohexylamino, etc., and preferredamong them are N-methylamino, N-ethylamino, N-propylamino,N-isopropylamino, N-butylamino, N-isobutylamino, N-tert-butylamino, etc.

[0063] As N,N-di-C₁-C₆ alkylamino groups, groups wherein an amino groupis N,N-disubstituted with alkyl groups having 1 to 6 carbon atoms arepreferred, and there can for example be mentioned N,N-dimethylamino,N,N-diethylamino, N,N-dipropylamino, N,N-diisopropylamino,N,N-dibutylamino, N,N-di-tert-butylamino, N,N-dipentylamino,N,N-dihexylamino, N-ethyl-N-methylamino, N-methyl-N-propylamino,N-isopropyl-N-methylamino, N-tert-butyl-N-methylamino,N-ethyl-N-isopropylamino, etc., and preferred among them areN,N-dimethylamino, N,N-diethylamino, N,N-diisopropylamino,N,N-dibutylamino, N,N-di-tert-butylamino, N-ethyl-N-methylamino,N-methyl-N-propylamino, N-isopropyl-N-methylamino,N-ethyl-N-isopropylamino, etc.

[0064] As N—C₁-C₁₀ alkycarbamoyl groups, groups wherein a carbamoylgroup is N-substituted with an alkyl group having 1 to 10 carbon atomsare preferred and there can for example be mentioned N-methylcarbamoyl,N-ethylcarbamoyl, N-propylcarbamoyl, N-isopropylcarbamoyl,N-butylcarbamoyl, N-isobutylcarbamoyl, N-sec-butylcarbamoyl,N-tert-butylcarbamoyl, N-pentylcarbamoyl, N-neopentyl-carbamoyl,N-hexylcarbamoyl, N-isohexylcarbamoyl, N-octylcarbamoyl,N-decylcarbamoyl, etc., and preferred among them are N-methylcarbamoyl,N-ethylcarbamoyl, N-propylcarbamoyl, N-isopropylcarbamoyl,N-isobutylcarbamoyl, N-sec-butylcarbamoyl, N-tert-butylcarbamoyl,N-octylcarbamoyl, N-decylcarbamoyl, etc.

[0065] As N,N-di-C₁-C₁₀ alkycarbamoyl groups, groups wherein a carbamoylgroup is N,N-disubstituted with alkyl groups having 1 to 10 carbon atomsare preferred, and there can for example be mentionedN,N-dimethylcarbamoyl, N,N-diethylcarbamoyl, N,N-dipropylcarbamoyl,N,N-diisopropylcarbamoyl, N,N-dibutylcarbamoyl.N,N-di-tert-butylcarbamoyl, N,N-dipentylcarbamoyl, N,N-dihexylcarbamoyl,N-ethyl-N-methylcarbamoyl, N-isopropyl-N-methylcarbamoyl,N-tert-butyl-N-methylcarbamoyl, N-ethyl-N-isopropylcarbamoyl, etc., andpreferred among them are N,N-dimethylcarbamoyl, N,N-diethylcarbamoyl,N,N-diisopropylcarbamoyl, N,N-dibutylcarbamoyl,N,N-di-tert-butylcarbamoyl, N-ethyl-N-methylcarbamoyl,N-isopropyl-N-methylcarbamoyl, N-ethyl-N-isopropylcarbamoyl, etc.

[0066] As N—C₁-C₁₀ alkythiocarbamoyl groups, groups wherein athiocarbamoyl group is N-substituted with an alkyl group having 1 to 10carbon atoms are preferred, and there can for example be mentionedN-methylthiocarbamoyl, N-ethylthiocarbamoyl, N-propylthiocarbamoyl,N-isopropylthiocarbamoyl, N-butylthiocarbamoyl, N-isobutylthiocarbamoyl,N-sec-butylthiocarbamoyl, N-tert-butylthiocarbamoyl,N-pentylthiocarbamoyl, N-neopentylthiocarbamoyl, N-hexylthiocarbamoyl,N-isohexylthiocarbamoyl, N-octylthiocarbamoyl, N-decylthiocarbamoyl,etc., and preferred among them are N-methylthiocarbamoyl,N-ethylthiocarbamoyl, N-propylthiocarbamoyl, N-isopropylthiocarbamoyl,N-isobutylthiocarbamoyl, N-sec-butylthiocarbamoyl,N-tert-butylthiocarbamoyl, N-octylthiocarbamoyl, N-decylthiocarbamoyl,etc.

[0067] As N,N-di-C₁-C₁₀ alkythiocarbamoyl groups, groups wherein athiocarbamoyl group is N,N-disubstituted with alkyl groups having 1 to10 carbon atoms are preferred, and there can for example be mentionedN,N-dimethylthiocarbamoyl, N,N-diethylthiocarbamoyl,N,N-dipropylthiocarbamoyl, N,N-diisopropylthiocarbamoyl,N,N-dibutylthiocarbamoyl, N,N-di-tert-butylthiocarbamoyl,N,N-dipentylthio-carbamoyl, N,N-dihexylthiocarbamoyl,N-ethyl-N-methylthiocarbamoyl, N-isopropyl-N-methylthiocarbamoyl,N-tert-butyl-N-methylthiocarbamoyl, N-ethyl-N-isopropyl-thiocarbamoyl,etc., and preferred among them are N,N-dimethylthiocarbamoyl,N,N-diethylthiocarbamoyl, N,N-diisopropylthiocarbamoyl,N,N-dibutylthiocarbamoyl, N,N-di-tert-butylthiocarbamoyl,N-ethyl-N-methylthiocarbamoyl, N-isopropyl-N-methylthiocarbamoyl,N-ethyl-N-isopropylthiocarbamoyl, etc.

[0068] As N-amino C₁-C₁₀ alkylcarbamoyl groups, groups wherein acarbamoyl group is N-substituted with an aminoalkyl group having 1 to 10carbon atoms are preferred, and there can for example be mentionedN-aminomethylcarbamoyl, N-aminoethylcarbamoyl, N-aminopropylcarbamoyl,N-aminomethylethylcarbamoyl, N-aminobutylcarbamoyl,N-aminopropylcarbamoyl, N-aminopentylcarbamoyl, N-aminohexylcarbamoyl,etc., and preferred among them are N-aminomethylcarbamoyl,N-aminoethylcarbamoyl, N-aminopropylcarbamoyl,N-aminomethylethylcarbamoyl, etc.

[0069] As N—C₁-C₆ alkoxy C₁-C₁₀ alkylcarbamoyl groups, groups wherein anN—C₁-C₁₀ alkylcarbamoyl group is substituted with an alkoxy having 1 to6 carbon atoms are preferred, and there can for example be mentionedN-methoxymethylcarbamoyl, N-methoxyethylcarbamoyl,N-methoxypropylcarbamoyl, N-methoxybutylcarbamoyl,N-ethoxypentylcarbamoyl, N-butoxyhexylcarbamoyl, etc., and preferredamong them are N-methoxymethylcarbamoyl, N-methoxyethylcarbamoyl,N-methoxypropylcarbamoyl, N-methoxybutylcarbamoyl, etc.

[0070] As N—C₁-C₆ alkoxycarbonyl C₁-C₁₀ alkylcarbamoyl groups, groupswherein the above-mentioned N—C₁-C₁₀ alkylcarbamoyl group is substitutedwith an alkoxycarbonyl having 1 to 6 carbon atoms are preferred, andthere can for example be mentioned N-methoxycarbonylmethylcarbamoyl,N-methoxycarbonylethylcarbamoyl, N-methoxycarbonylpropylcarbamoyl,N-methoxycarbonylbutylcarbamoyl, N-ethoxy-carbonylpentylcarbamoyl,N-butoxycarbonylhexylcarbamoyl, N-tert-butoxycarbonyl-ethylcarbamoyl,etc., and preferred among them are N-methoxycarbonylmethyl-carbamoyl,N-methoxycarbonylethylcarbamoyl, N-methoxycarbonylpropylcarbamoyl,N-methoxycarbonylbutylcarbamoyl, N-tert-butoxycarbonylethylcarbamoyl,etc.

[0071] As amino C₁-C₆ alkoxycarbonyl groups, groups wherein a carbonylgroup is substituted with an aminoalkoxy group having 1 to 6 carbonatoms are preferred, and there can for example be mentionedaminomethoxycarbonyl, aminoethoxycarbonyl, aminopropoxycarbonyl,2-amino-2-methylpropoxycarbonyl, 2-aminomethylethoxy-carbonyl,aminobutoxycarbonyl, 2-aminopropoxycarbonyl, aminopentyloxycarbonyl.aminohexyloxycarbonyl, etc., and preferred among them areaminomethoxycarbonyl, aminoethoxycarbonyl, aminopropoxycarbonyl,2-aminomethylethoxycarbonyl, 2-amino-2-methylpropoxycarbonyl, etc.

[0072] As N—C₁-C₆ alkoxycarbonylamino C₁-C₁₀ alkylcarbamoyl groups,groups wherein the above-mentioned N—C₁-C₁₀ alkylcarbamoyl group issubstituted with an alkoxycarbonylamino group having 1 to 6 carbon atomsare preferred, and there can for example be mentionedN-methoxycarbonylaminomethylcarbamoyl,N-methoxycarbonylaminoethylcarbamoyl,N-methoxycarbonylaminopropylcarbamoyl,N-methoxycarbonylaminobutylcarbamoyl,N-ethoxycarbonylaminopentylcarbamoyl,N-butoxycarbonylaminohexylcarbamoyl,N-tert-butoxycarbonylaminohexylcarbamoyl, etc., and preferred among themare N-methoxycarbonylaminomethylcarbamoyl,N-methoxycarbonylaminoethylcarbamoyl,N-methoxycarbonylaminopropylcarbamoyl,N-methoxycarbonylaminobutylcarbamoyl,N-tert-butoxycarbonylaminoethyl-carbamoyl, etc.

[0073] As N—C₁-C₆ alkoxycarbonylamino C₁-C₆ alkoxycarbonyl groups,groups wherein a C₁-C₆ alkoxycarbonyl group is substituted with anN-alkoxycarbonylamino group having 1 to 6 carbon atoms are preferred,and there can for example be mentionedN-methoxycarbonylaminomethoxycarbonyl,N-methoxycarbonylaminoethoxycarbonyl,N-methoxycarbonylaminopropoxycarbonyl,N-methoxycarbonylaminobutoxycarbonyl,N-ethoxycarbonylaminopentyloxycarbonyl,N-butoxycarbonylaminohexyloxycarbonyl,N-tert-butoxycarbonylaminoethoxycarbonyl, etc., and preferred among themare N-methoxycarbonylaminomethoxycarbonyl,N-methoxycarbonylaminoethoxycarbonyl,N-methoxycarbonylaminopropoxycarbonyl,N-methoxycarbonylaminobutoxycarbonyl,N-tert-butoxycarbonylaminoethoxycarbonyl, etc.

[0074] As N—C₂-C₆ alkenylcarbamoyl groups, groups wherein a carbamoylgroup is N-substituted with an alkenyl group having 2 to 6 carbon atomsare preferred, and there can for example be mentioned N-vinylcarbamoyl,N-allylcarbamoyl, N-(1-propenyl)carbamoyl, N-isopropenylcarbamoyl,N-(2-butenyl)carbamoyl, N-isobutenylcarbamoyl, N-(2-pentenyl)carbamoyl,N-(2-hexenyl)carbamoyl, N-(2-heptenyl)carbamoyl, N-(2-octenyl)carbamoyl,etc., and preferred among them are N-vinylcarbamoyl, N-allylcarbamoyl,N-(1-propenyl)carbamoyl, etc.

[0075] As N,N-di-C₂-C₆ alkenylcarbamoyl groups, groups wherein acarbamoyl group is N,N-disubstituted with alkenyl groups having 2 to 6carbon atoms are preferred, and there can for example be mentionedN,N-divinylcarbamoyl, N,N-diallylcarbamoyl,N,N-di-(1-propenyl)carbamoyl, N,N-diisopropenylcarbamoyl,N-allyl-N-vinyl-carbamoyl, N-allyl-N-isobutenylcarbamoyl,N-allyl-N-(2-pentenyl)carbamoyl, N-allyl-N-(2-hexenyl)carbamoyl,N-allyl-N-(2-heptenyl)carbamoyl, N-allyl-N-(2-octenyl)-carbamoyl, etc.,and preferred among them are N-allyl-N-vinylcarbamoyl,N,N-diallylcarbamoyl, N-allyl-N-(1-propenyl)carbamoyl, etc.

[0076] As N—C₁-C₆ alkylsulfamoyl groups, groups wherein a sulfamoyl isN-substituted with an alkyl group having 1 to 6 carbon atoms arepreferred, and there can for example be mentioned N-methylsulfamoyl,N-ethylsulfamoyl, N-propylsulfamoyl, N-isopropylsulfamoyl,N-butylsulfamoyl, N-isobutylsulfamoyl, N-sec-butylsulfamoyl,N-tert-butylsulfamoyl, N-pentylsulfamoyl, N-neopentylsulfamoyl,N-hexylsulfamoyl, N-isohexylsulfamoyl, etc., and preferred among themare N-methylsulfamoyl, N-ethylsulfamoyl, N-isopropylsulfamoyl,N-tert-butylsulfamoyl, etc.

[0077] As N,N-di-C₁-C₆ alkylsulfamoyl groups, groups wherein a sulfamoylis N,N-disubstituted with alkyl groups having 1 to 6 carbon atoms arepreferred, and there can for example be mentioned N,N-dimethylsulfamoyl,N,N-diethylsulfamoyl, N,N-dipropylsulfamoyl, N,N-diisopropylsulfamoyl,N,N-dibutylsulfamoyl, N,N-di-tert-butylsulfamoyl, N,N-dipentylsulfamoyl,N,N-dihexylsulfamoyl, N-ethyl-N-methylsulfamoyl,N-isopropyl-N-methylsulfamoyl, N-tert-butyl-N-methylsulfamoyl,N-ethyl-N-isopropylsulfamoyl, etc., and preferred among them areN,N-dimethylsulfamoyl, N,N-diethylsulfamoyl, N,N-diisopropylsulfamoyl,N,N-dibutylsulfamoyl, N,N-di-tert-butylsulfamoyl,N-ethyl-N-methylsulfamoyl, N-isopropyl-N-methylsulfamoyl,N-ethyl-N-isopropylsulfamoyl, etc.

[0078] As C₁-C₆ alkylsulfinyl groups, groups wherein a sulfinyl group issubstituted with an alkyl group having 1 to 6 carbon atoms arepreferred, and there can for example be mentioned methylsulfinyl,ethylsulfinyl, propylsulfinyl, isopropylsulfinyl, butylsulfinyl,isobutylsulfinyl, sec-butylsulfinyl, tert-butylsulfinyl, pentylsulfinyl,neopentylsulfinyl, hexylsulfinyl, isohexylsulfinyl, etc., and preferredamong them are methylsulfinyl, ethylsulfinyl, propylsulfinyl,isopropylsulfinyl, butylsulfinyl, tert-butylsulfinyl, etc.

[0079] As C₁-C₆ alkylsulfonyl groups, groups wherein a sulfonyl group issubstituted with an alkyl group having 1 to 6 carbon atoms arepreferred, and there can for example be mentioned methylsulfonyl,ethylsulfonyl, propylsulfonyl, isopropylsulfonyl, butylsulfonyl,isobutylsulfonyl, sec-butylsulfonyl, tert-butylsulfonyl, pentylsulfonyl,neopentylsulfonyl, hexylsulfonyl, isohexylsulfonyl, etc., and preferredamong them are methylsulfonyl, ethylsulfonyl, propylsulfonyl,butylsulfonyl, tert-butylsulfonyl, etc.

[0080] As C₁-C₆ alkylsulfonylamino groups, groups wherein an amino groupis substituted with an alkylsulfonyl group having 1 to 6 carbon atomsare preferred, and there can for example be mentionedN-methylsulfonylamino, N-ethylsulfonylamino, N-propylsulfonylamino,N-isopropylsulfonylamino, N-butylsulfonylamino, N-isobutylsulfonylamino,N-sec-butylsulfonylamino, N-tert-butylsulfonylamino,N-pentylsulfonylamino, N-neopentylsulfonylamino, N-hexylsulfonylamino,N-isohexylsulfonylamino, etc., and preferred among them areN-methylsulfonylamino, N-ethylsulfonylamino, N-propylsulfonylamino,N-butylsulfonylamino, N-tert-butylsulfonylamino, etc.

[0081] As C₁-C₆ alkylthio groups, groups wherein a sulfur atom issubstituted with an alkyl group having 1 to 6 carbon atoms arepreferred, and there can for example be mentioned methylthio, ethylthio,propylthio, isopropylthio, butylthio, isobutylthio, sec-butylthio,tert-butylthio, pentylthio, neopentylthio, hexylthio, isohexylthio,etc., and preferred among them are methylthio, ethylthio, propylthio,isopropylthio. butylthio, tert-butylthio, etc.

[0082] As C₁-C₆ alkoxy groups, groups wherein an oxygen atom issubstituted with an alkyl group having 1 to 6 carbon atoms arepreferred, and there can for example be mentioned methoxy, ethoxy,propoxy, isopropoxy, butoxy, isobutoxy, sec-butoxy, tert-butoxy,pentyloxy, neopentyloxy, hexyloxy, isohexyloxy, etc., and preferredamong them are methoxy, ethoxy, propoxy, isopropoxy, butoxy, isobutoxy,tert-butoxy, etc.

[0083] As C₁-C₆ alkoxycarbonyl groups, groups wherein a carbonyl groupis substituted with an alkoxy group having 1 to 5 carbon atoms arepreferred, and there can for example be mentioned methoxycarbonyl,ethoxycarbonyl, propoxycarbonyl, isopropoxycarbonyl, butoxycarbonyl,isobutoxycarbonyl, sec-butoxycarbonyl, tert-butoxycarbonyl,pentyoxycarbonyl, neopentyoxycarbonyl, etc., and preferred among themare methoxycarbonyl, ethoxycarbonyl, propoxycarbonyl,isopropoxycarbonyl, butoxycarbonyl, tert-butoxycarbonyl, etc.

[0084] As N—C₃-C₆ cycloalkylamino groups, groups wherein an amino groupis N-substituted with a cyclic alkyl group having 3 to 6 carbon atomsare preferred, and there can for example be mentionedN-cyclopropylamino, N-cyclobutylamino, N-cyclopentylamino,N-cyclohexylamino, etc., and preferred among them areN-cyclopropylamino, N-cyclopentylamino, N-cyclohexylamino, etc.

[0085] As N,N-di-C₃-C₆ cycloalkylamino groups, groups wherein an aminogroup is N,N-disubstituted with cyclic alkyl groups having 3 to 6 carbonatoms are preferred, and there can for example be mentionedN,N-dicyclopropylamino, N,N-dicyclobutylamino, N,N-dicyclopentylamino,N,N-dicyclohexylamino, N-cyclobutyl-N-cyclopropylamino,N-cyclopentyl-N-cyclopropylamino, N-cyclohexyl-N-cyclopropylamino, etc.,and preferred among them are N,N-dicyclopropylamino,N,N-dicyclobutylamino, N,N-dicyclopentylamino, etc.

[0086] As C₃-C₆ cycloalkyloxy groups, groups wherein an oxygen atom issubstituted with a cyclic alkyl group having 3 to 6 carbon atoms arepreferred, and there can for example be mentioned cyclopropoxy,cyclobutoxy, cyclopentyloxy, cyclohexyloxy, etc., and preferred amongthem are cyclopropoxy, cyclopentyloxy, cyclohexyloxy etc.

[0087] As N—C₃-C₆ cycloalkycarbamoyl groups, groups wherein a carbamoylgroup is N-substituted with a cyclic alkyl group having 3 to 6 carbonatoms are preferred, and there can for example be mentionedN-cyclopropylcarbamoyl, N-cyclobutylcarbamoyl, N-cyclopentylcarbamoyl,N-cyclohexylcarbamoyl, etc., and preferred among them areN-cyclopropylcarbamoyl, N-cyclopentylcarbamoyl, N-cyclohexylcarbamoyl.etc.

[0088] As N,N-di-C₃-C₆ cycloalkycarbamoyl groups, groups wherein acarbamoyl group is N,N-disubstituted with cyclic alkyl groups having 3to 6 carbon atoms are preferred. and there can for example be mentionedN,N-dicyclopropylcarbamoyl, N,N-dicyclobutylcarbamoyl,N,N-dicyclopentylcarbamoyl, N,N-dicyclohexylcarbamoyl,N-cyclobutyl-N-cyclopropylcarbamoyl,N-cyclopentyl-N-cyclopropylcarbamoyl,N-cyclohexyl-N-cyclopropylcarbamoyl, etc., and preferred among them areN,N-dicyclopropylcarbamoyl, N,N-dicyclobutylcarbamoyl,N,N-dicyclopentylcarbamoyl, etc.

[0089] As saturated C₁-C₉ aliphatic groups, alkyl groups having 1 to 9carbon atoms are preferred, and they may be straight-chain or branched.Among them straight-chain or branched alkyl groups having 1 to 6 carbonatoms are preferred.

[0090] As the alkyl groups, there can for example be mentioned methyl,ethyl, propyl, isopropyl, butyl, isobutyl, sec-butyl, tert-butyl,pentyl, neopentyl, hexyl, isohexyl, heptyl, octyl, nonyl, etc., andpreferred among them are methyl, ethyl, propyl, isopropyl, isobutyl,sec-butyl, tert-butyl, etc.

[0091] As unsaturated C₁-C₉ aliphatic groups, alkenyl groups or alkynylgroups each having 1 to 9 carbon atoms are preferred, and they may bestraight-chain or branched. Among them straight-chain or branchedalkenyl groups or alkynyl groups each having 1 to 6 carbon atoms arepreferred.

[0092] As the alkenyl groups, there can for example be mentioned vinyl,allyl, 1-propenyl, isopropenyl, 2-butenyl, isobutenyl, 2-pentenyl,2-hexenyl, 2-heptenyl, 2-octenyl, etc., and preferred among them arevinyl, allyl, 1-propenyl, etc.

[0093] As the alkynyl groups, there can for example be mentionedethynyl, 1-propynyl, 1-butenyl, 1-pentenyl, 1-hexynyl, 1-heptynyl,1-octynyl, etc., and preferred among them are ethynyl, 1-propynyl, etc.

[0094] As 5- or 6-membered saturated carbocyclic groups, there can forexample be mentioned cyclopentyl, cyclohexyl, etc., and preferred amongthem are cyclopentyl, etc.

[0095] As 5- or 6-membered unsaturated carbocyclic groups, there can forexample be mentioned cyclopentenyl, cyclohexenyl, etc., and preferredamong them are cyclopentenyl, etc.

[0096] As N—C₁-C₁₀ alkylcarbamoyl groups, N—C₁-C₁₀ alkylthiocarbamoylgroups, thiocarbonyl groups or carbonyl groups each substituted with a5- or 6-membered heterocyclic group, N—C₁-C₁₀ alkylcarbamoyl groups,N—C₁-C₁₀ alkylthiocarbamoyl groups, thiocarbonyl groups or carbonylgroups each substituted with the above-mentioned heterocyclic group arepreferred, and there can for example be mentionedN-isoxazolylalkylcarbamoyl such as N-isoxazolylmethylcarbamoyl,N-isothiazolyl-alkylcarbamoyl such as N-isothiazolylmethylcarbamoyl,N-imidazolylalkylcarbamoyl such as N-imidazolylmethylcarbamoyl,N-oxazolylalkylcarbamoyl such as N-oxazolyl-methylcarbamoyl,N-oxadiazolylalkylcarbamoyl such as N-oxadiazolylmethyl-carbamoyl,N-thiazolylalkylcarbamoyl such as N-thiazolylmethylcarbamoyl,N-thiadiazolylalkylcarbamoyl such as N-thiadiazolylmethylcarbamoyl,N-thienyl-alkylcarbamoyl such as N-thienylmethylcarbamoyl,N-triazinylalkylcarbamoyl such as N-triazinylmethylcarbamoyl,N-triazolylalkylcarbamoyl such as N-triazolylmethyl-carbamoyl,N-pyridylalkylcarbamoyl such as N-pyridylmethylcarbamoyl,N-pyrazinyl-alkylcarbamoyl such as N-pyrazinylmethylcarbamoyl,N-pyrimidinylalkylcarbamoyl such as N-pyrimidinylmethylcarbamoyl,N-pyridazinylalkylcarbamoyl such as N-pyridazinylmethylcarbamoyl,N-pyrazolylalkylcarbamoyl such as N-pyrazolylmethyl-carbamoyl,N-pyrrolylalkylcarbamoyl such as N-pyrrolylmethylcarbamoyl,N-pyranylalkylcarbamoyl such as N-pyranylmethylcarbamoyl,N-furylalkylcarbamoyl such as N-furylmethylcarbamoyl,N-furazanylalkylcarbamoyl such as N-furazanyl-methylcarbamoyl,N-imidazolidinylalkylcarbamoyl such as N-imidazolidinylmethyl-carbamoyl,N-imidazolinylalkylcarbamoyl such as N-imidazolinylmethylcarbamoyl,N-tetrahydrofuranylalkylcarbamoyl such asN-tetrahydrofuranylalkylcarbamoyl, N-pyrazolidinylalkylcarbamoyl such asN-pyrazolidinylmethylcarbamoyl, N-pyrazolinyl-alkylcarbamoyl such asN-pyrazolinylmethylcarbamoyl, N-piperazinylalkylcarbamoyl such asN-piperazinylmethylcarbamoyl, N-piperidinylalkylcarbamoyl such asN-piperidinylmethylcarbamoyl, N-pyrrolidinylalkylcarbamoyl such asN-pyrrolidinyl-methylcarbamoyl, N-pyrrolinylalkylcarbamoyl such asN-pyrrolinylmethylcarbamoyl, N-morpholinoalkylcarbamoyl such asN-morpholinomethylcarbamoyl; for example, N-isoxazolylalkylthiocarbamoylsuch as N-isoxazolylmethylthiocarbamoyl,N-isothiazolylalkylthiocarbamoyl such asN-isothiazolylmethylthiocarbamoyl, N-imidazolylalkylthiocarbamoyl suchas N-imidazolylmethylthiocarbamoyl, N-oxazolylalkylthiocarbamoyl such asN-oxazolylmethylthiocarbamoyl, N-oxadiazolyl-alkylthiocarbamoyl such asN-oxadiazolylmethylthiocarbamoyl, N-thiazolylalkyl-thiocarbamoyl such asN-thiazolylmethylthiocarbamoyl N-thiadiazolylalkyl-thiocarbamoyl such asN-thiadiazolylmethylthiocarbamoyl, N-thienylalkylthio-carbamoyl such asN-thienylmethylthiocarbamoyl, N-triazinylalkylthiocarbamoyl such asN-triazinylmethylthiocarbamoyl, N-triazolylalkylthiocarbamoyl such asN-triazolylmethylthiocarbamoyl, N-pyridylalkylthiocarbamoyl such asN-pyridyl-methylthiocarbamoyl, N-pyrazinylalkylthiocarbamoyl such asN-pyrazinylmethyl-thiocarbamoyl, N-pyrimidinylalkylthiocarbamoyl such asN-pyrimidinylmethylthio-carbamoyl, N-pyridazinylalkylthiocarbamoyl suchas N-pyridazinylmethylthio-carbamoyl, N-pyrazolylalkylthiocarbamoyl suchas N-pyrazolylmethylthiocarbamoyl, N-pyrrolylalkylthiocarbamoyl such asN-pyrrolylmethylthiocarbamoyl, N-pyranyl-alkylthiocarbamoyl such asN-pyranylmethylthiocarbamoyl, N-furylalkylthio-carbamoyl such asN-furylmethylthiocarbamoyl, N-furazanylalkylthiocarbamoyl such asN-furazanylmethylthiocarbamoyl, N-imidazolidinylalkylthiocarbamoyl suchas N-imidazolidinylmethylthiocarbamoyl, N-imidazolinylalkylthiocarbamoylsuch as N-imidazolinylmethylthiocarbamoyl,N-tetrahydrofuranylalkylthiocarbamoyl such asN-tetrahydrofuranylalkylthiocarbamoyl, N-pyrazolidinylalkylthiocarbamoylsuch as N-pyrazolidinylmethylthiocarbamoyl.N-pyrazolinylalkylthiocarbamoyl such asN-pyrazolinylmethylthiocarbamoyl, N-piperazinylalkylthiocarbamoyl suchas N-piperazinylmethylthiocarbamoyl, N-piperidinylalkylthiocarbamoylsuch as N-piperidinylmethylthiocarbamoyl,N-pyrrolidinylalkylthiocarbamoyl such asN-pyrrolidinylmethylthiocarbamoyl, N-pyrrolinylalkylthiocarbamoyl suchas N-pyrrolinylmethylthiocarbamoyl. N-morpholinoalkylthiocarbamoyl suchas N-morpholinomethylthiocarbamoyl, etc.; for example,isoxazolylthiocarbonyl, isothiazolylthiocarbonyl,imidazolylthiocarbonyl, oxazolylthiocarbonyl, oxadiazolyl-thiocarbonyl,thiazolylthiocarbonyl, thiadiazolylthiocarbonyl, thienylthiocarbonyl,triazinylthiocarbonyl, triazolylthiocarbonyl, pyridylthiocarbonyl,pyrazinylthio-carbonyl, pyrimidinylthiocarbonyl,pyridazinylthiocarbonyl, pyrazolylthiocarbonyl, pyrrolylthiocarbonyl,pyranylthiocarbonyl, furylthiocarbonyl, furazanylthiocarbonyl,imidazolidinylthiocarbonyl, imidazolinylthiocarbonyl,tetrahydrofuranylthiocarbonyl, pyrazolidinylthiocarbonyl,pyrazolinylthiocarbonyl, piperazinylthiocarbonyl,piperidinylthiocarbonyl, pyrrolidinylthiocarbonyl,pyrrolinylthiocarbonyl, morpholinothiocarbonyl, etc.; for example,isoxazolylcarbonyl, isothiazolylcarbonyl, imidazolylcarbonyl,oxazolylcarbonyl, oxadiazolylcarbonyl, thiazolylcarbonyl,thiadiazolylcarbonyl, thienylcarbonyl, triazinylcarbonyl,triazolylcarbonyl, pyridylcarbonyl, pyrazylcarbonyl, pyrazinylcarbonyl,pyrimidinylcarbonyl, pyridazinylcarbonyl, pyrazolylcarbonyl,pyrrolylcarbonyl, pyranylcarbonyl, furylcarbonyl, furazanylcarbonyl,imidazolidinylcarbonyl, imidazolinylcarbonyl, tetrahydrofuranylcarbonyl,pyrazolidinylcarbonyl, pyrazolinylcarbonyl, piperazinyl-carbonyl,piperidinylcarbonyl, pyrrolidinylcarbonyl, pyrrolinylcarbonyl,morpholino-carbonyl, etc., and preferred among them are N—C₁-C₁₀alkylcarbamoyl groups, N—C₁-C₁₀ alkylthiocarbamoyl groups, athiocarbonyl group or a carbonyl group, etc. each substituted forexample with thienyl, pyridyl, pyrazinyl, pyrimidinyl, furyl,tetrahydrofuranyl, morpholino or the like.

[0097] N—C₁-C₁₀ alkylcarbamoyl groups, N—C₁-C₁₀ alkylthiocarbamoylgroups, thiocarbonyl groups or carbonyl groups each substituted with amonocyclic to tricyclic aromatic heterocyclic group (excluding 5- or6-membered heterocyclic groups) having per one ring 1 to 5 hetero atomsselected from the group consisting of a nitrogen atom, an oxygen atomand a sulfur atom mean N—C₁-C₁₀ alkylcarbamoyl groups, N—C₁-C₁₀alkylthiocarbamoyl groups, thiocarbonyl groups or carbonyl groups eachsubstituted with the above-mentioned aromatic heterocyclic group, andthere can for example be mentioned N-acridinylalkylcarbamoyl such asN-acridinylmethylcarbamoyl, N-isoquinolylalkylcarbamoyl such asN-isoquinolylmethylcarbamoyl, N-isoindolylalkyl-carbamoyl such asN-isoindolylmethylcarbamoyl, N-indazolylalkylcarbamoyl such asN-indazolylmethylcarbamoyl, N-indolylalkylcarbamoyl such asN-indolylmethyl-carbamoyl, N-indolizinylalkylcarbamoyl such asN-indolizinylmethylcarbamoyl, N-ethylenedioxyphenylalkylcarbamoyl suchas N-ethylenedioxyphenylmethylcarbamoyl, N-carbazolylalkylcarbamoyl suchas N-carbazolylmethylcarbamoyl, N-quinazolinyl-alkylcarbamoyl such asN-quinazolinylmethylcarbamoyl, N-quinoxalinylalkyl-carbamoyl such asN-quinoxalinylmethylcarbamoyl, N-quinolizinylalkylcarbamoyl such asN-quinolizinylmethylcarbamoyl, N-quinolylalkylcarbamoyl such asN-quinolylmethylcarbamoyl, N-cumaronylalkylcarbamoyl such asN-cumaronylmethyl-carbamoyl, N-chromenylalkylcarbamoyl such asN-chromenylmethylcarbamoyl, N-phenanthridinylalkylcarbamoyl such asN-phenanthridinylmethylcarbamoyl, N-phenanthrolinylalkylcarbamoyl suchas N-phenanthrolinylmethylcarbamoyl, N-dibenzofuranylalkylcarbamoyl suchas N-dibenzofuranylmethylcarbamoyl, N-dibenzothiophenylalkylcarbamoylsuch as N-dibenzothiophenylmethylcarbamoyl, N-cinnolinylalkylcarbamoylsuch as N-cinnolinylmethylcarbamoyl, N-thionaphthenyl-alkylcarbamoylsuch as N-thionaphthenylmethylcarbamoyl, N-naphthyridinylalkyl-carbamoylsuch as N-naphthyridinylmethylcarbamoyl, N-phenazinylalkylcarbamoyl suchas N-phenazinylmethylcarbamoyl, N-phenoxazinylalkylcarbamoyl such asN-phenoxazinylmethylcarbamoyl, N-phenothiazinylalkylcarbamoyl such asN-phenothiazinylmethylcarbamoyl, N-phthalazinylalkylcarbamoyl such asN-phthalazinylmethylcarbamoyl, N-pteridinylalkylcarbamoyl such asN-pteridinyl-methylcarbamoyl, N-purinylalkylcarbamoyl such asN-purinylmethylcarbamoyl, N-benzimidazolylalkylcarbamoyl such asN-benzimidazolylmethylcarbamoyl, N-benzoxazolylalkylcarbamoyl such asN-benzoxazolylmethylcarbamoyl, N-benzothiazolylalkylcarbamoyl such asN-benzothiazolylmethylcarbamoyl, N-benzotriazolylalkylcarbamoyl such asN-benzotriazolylmethylcarbamoyl, N-benzofuranylalkylcarbamoyl such asN-benzofuranylmethylcarbamoyl, N-methylenedioxyphenylalkylcarbamoyl suchas N-methylenedioxyphenylmethyl-carbamoyl, etc.; for example,N-acridinylalkylthiocarbamoyl such as N-acridinylmethylthiocarbamoyl,N-isoquinolylalkylthiocarbamoyl such asN-isoquinolylmethylthiocarbamoyl, N-isoindolylalkylthiocarbamoyl such asN-isoindolylmethylthiocarbamoyl, N-indazolylalkylthiocarbamoyl such asN-indazolylmethylthiocarbamoyl, N-indolylalkylthiocarbamoyl such asN-indolylmethylthiocarbamoyl, N-indolizinylalkylthiocarbamoyl such asN-indolizinylmethylthiocarbamoyl,N-ethylenedioxyphenylalkylthiocarbamoyl such asN-ethylenedioxyphenylmethylthiocarbamoyl, N-carbazolylalkylthiocarbamoylsuch as N-carbazolylmethylthiocarbamoyl,N-quinazolinylalkylthiocarbamoyl such asN-quinazolinylmethylthiocarbamoyl, N-quinoxalinylalkylthiocarbamoyl suchas N-quinoxalinylmethylthiocarbamoyl, N-quinolidinylalkylthiocarbamoylsuch as N-quinolidinylmethylthiocarbamoyl, N-quinolylalkylthiocarbamoylsuch as N-quinolylmethylthiocarbamoyl, N-cumaronylalkylthiocarbamoylsuch as N-cumaronylmethylthiocarbamoyl, N-chromenylalkylthiocarbamoylsuch as N-chromenylmethylthiocarbamoyl,N-phenanthridinylalkylthiocarbamoyl such asN-phenanthridinylmethylthiocarbamoyl,N-phenanthrolinylalkylthiocarbamoyl such asN-phenanthrolinylmethylthiocarbamoyl, N-dibenzofuranylalkylthiocarbamoylsuch as N-dibenzofuranylmethylthiocarbamoyl,N-dibenzothiophenylalkylthiocarbamoyl such asN-dibenzothiophenylmethylthiocarbamoyl, N-cinnolinylalkylthiocarbamoylsuch as N-cinnolinylmethylthiocarbamoyl,N-thionaphthenylalkylthiocarbamoyl such asN-thionaphthenylmethylthiocarbamoyl, N-naphthyridinylalkylthiocarbamoylsuch as N-naphthyridinylmethylthiocarbamoyl,N-phenazinylalkylthiocarbamoyl such as N-phenazinylmethylthiocarbamoyl,N-phenoxazinylalkylthiocarbamoyl such asN-phenoxazinylmethylthiocarbamoyl, N-phenothiazinylalkylthiocarbamoylsuch as N-phenothiazinylmethylthiocarbamoyl,N-phthalazinylalkylthiocarbamoyl such asN-phthalazinylmethylthiocarbamoyl, N-pteridinylalkylthiocarbamoyl suchas N-pteridinylmethylthiocarbamoyl, N-purinylalkylthiocarbamoyl such asN-purinylmethylthiocarbamoyl, N-benzimidazolylalkylthiocarbamoyl such asN-benzimidazolylmethylthiocarbamoyl, N-benzoxazolylalkylthiocarbamoylsuch as N-benzoxazolylmethylthiocarbamoylN-benzothiazolylalkylthiocarbamoyl such asN-benzothiazolylmethylthiocarbamoyl, N-benzotriazolytalkylthiocarbamoylsuch as N-benzotriazolylmethylthiocarbamoyl,N-benzofuranylalkylthiocarbamoyl such asN-benzofuranylmethylthiocarbamoyl,N-methylenedioxyphenylalkylthiocarbamoyl such asN-methylenedioxyphenylmethylthiocarbamoyl, etc.; for example,acridinyl-thiocarbonyl, isoquinolylthiocarbonyl, isoindolylthiocarbonyl,indazolylthiocarbonyl, indolylthiocarbonyl, indolizinylthiocarbonyl,ethylenedioxyphenylthiocarbonyl, carbazolylthiocarbonyl,quinazolinylthiocarbonyl, quinoxalinylthiocarbonyl,quinolizinylthiocarbonyl, quinolylthiocarbonyl, cumaronylthiocarbonyl,chromenylthiocarbonyl, phenanthridinylthiocarbonyl,phenanthrolinylthiocarbonyl, dibenzofuranylthiocarbonyl,dibenzothiphenylthiocarbonyl, cinnolinylthiocarbonyl,thionaphthenylthiocarbonyl, naphthyridinylthiocarbonyl,phenazinylthiocarbonyl, phenoxazinylthiocarbonyl,phenothiazinylthiocarbonyl, phthalazinylthiocarbonyl,pteridinylthiocarbonyl, purinylthiocarbonyl, benzimidazolylthiocarbonyl,benzoxazolylthiocarbonyl, benzothiazolylthiocarbonyl,benzotriazolylthiocarbonyl, benzofuranylthiocarbonyl,methylenedioxyphenylthiocarbonyl, etc.; for example, acridinylcarbonyl,isoquinolylcarbonyl, isoindolylcarbonyl, indazolylcarbonyl,indolylcarbonyl, indol izinylcarbonyl, ethylenedioxyphenylcarbonyl,carbazolyl-carbonyl, quinazolinylcarbonyl, quinoxalinylcarbonyl,quinolizinylcarbonyl, quinolylcarbonyl, cumaronylcarbonyl,chromenylcarbonyl, phenanthridinylcarbonyl, phenanthrolinylcarbonyl,dibenzofuranylcarbonyl, dibenzothiphenylcarbonyl, cinnolinylcarbonyl,thionaphthenylcarbonyl, naphthyridinylcarbonyl, phenazinyl-carbonyl,phenoxazinylcarbonyl, phenothiazinylcarbonyl, phthalazinylcarbonyl,pteridinylcarbonyl, purinylcarbonyl, benzimidazolylcarbonyl,benzoxazolylcarbonyl. benzothiazolylcarbonyl, benzotriazolylcarbonyl,benzofuranylcarbonyl. methylenedioxyphenylcarbonyl, etc., and preferredamong them are N—Cl-Clo alkylcarbamoyl groups, N—C₁-C₁₀alkylthiocarbamoyl groups, thiocarbonyl groups and carbonyl groups eachsubstituted for example with an ethylenedioxyphenyl group, adibenzofuranyl group, a dibenzothiophenyl group, a methylenedioxyphenylgroup or the like.

[0098] Condensed aryl groups mean groups wherein for example a phenylgroup or a naphthyl group is bound to another ring to form a condensedbenzene ring or a condensed naphthalene ring.

[0099] As di- or tricyclic saturated or unsaturated C₆-C₁₅ condensedcarbocyclic groups, there can for example be mentioned acenaphthylenyl,adamantyl, anthryl, indanyl, indenyl, C₆-C₈ cycloalkanyl, C₆-C₈cycloalkadienyl, C₆-C₈ cycloalkenyl, norbornyl, phenanthryl, fluorenyl,etc., and preferred among them are anthryl, C₆-C₈ cycloalkanyl, C₆-C₈cycloalkadienyl, C₆-C₈ cycloalkenyl, etc.

[0100] As the C₆-C₈ cycloalkanyl groups, there can for example bementioned cyclohexanyl, cycloheptanyl, cyclooctanyl, etc., and preferredamong them are cyclohexanyl, etc.

[0101] As the C₆-C₈ cycloalkadienyl groups, there can for example bementioned cyclohexadienyl, cycloheptadienyl, cyclooctadienyl, etc., andpreferred among them are cyclohexadienyl, etc.

[0102] As the C₆-C₈ cycloalkenyl groups, there can for example bementioned cyclohexenyl, cycloheptenyl, cyclooctenyl, etc., and preferredamong them are cyclohexenyl, etc.

[0103] As 6-membered heterocyclic groups, or di- or tricyclic condensedaromatic heterocyclic groups having per one ring 1 to 5 hetero atomsselected from the group consisting of nitrogen atoms, oxygen atoms andsurfur atoms, there can for example be mentioned isoquinolyl,isoindolyl, indazolyl, indolyl, indolizinyl, ethylenedioxyphenyl,quinazolinyl, quinoxalinyl, quinolizinyl, quinolyl, cumaronyl,chromenyl, thionaphthenyl, naphthyridinyl, pyridyl, pyrazinyl,pyrimidinyl, pyridazinyl, pyranyl, phthalazinyl, benzimidazolyl,benzoxazolyl, benzothiazolyl, benzotriazolyl, benzofuranyl,methylenedioxypheny, etc., and preferred among them areethylenedioxypheny, pyridyl, pyrazinyl, pyrimidinyl, pyridazinyl,benzimidazolyl, benzoxazolyl, benzothiazolyl, benzotriazolyl,benzofuranyl, methylenedioxypheny, etc. Particularly preferred areethylenedioxypheny, pyridyl, pyrazinyl, pyrimidinyl, pyridazinyl,methylenedioxypheny, etc.

[0104] R means, for example, an aryl group, a mono- to tricyclic C₇-C₁₅aromatic carbocyclic group, a 5- or 6-membered heterocyclic group, or amono- to tricyclic aromatic heterocyclic group having per one ring 1 to5 hetero atoms selected from the group consisting of nitrogen atoms,oxygen atoms and sulfur atoms, etc.

[0105] Specifically, as the aryl groups, aryl groups having 6 to 15carbon atoms are preferred, and there can for example be mentionednaphthyl, phenyl, etc., and preferred among them are pheny, etc.

[0106] As the mono- to tricyclic C₇-C₁₅ aromatic carbocyclic groups,aromatic groups having 7 to 15 carbon atoms and having 1 to 3 cyclicgroups are preferred, and there can for example be mentionedacenaphthylenyl, adamantyl, anthryl, indenyl, norbornyl, phenanthryl,etc., and preferred among them are anthryl, phenanthryl, etc.

[0107] As the 5- or 6-membered heterocyclic groups, there can forexample be mentioned the aforementioned series of groups A, etc., andpreferred among them are thienyl, tetrahydrofuranyl, pyridyl, pyrazinyl,pyrimidinyl, furyl, morpholino, etc.

[0108] As the mono- to tricyclic aromatic heterocyclic groups having perone ring 1 to 5 hetero atoms selected from the group consisting ofnitrogen atoms, oxygen atoms and surfur atoms, there can for example bementioned the aforementioned series of groups B, etc., and preferredamong them are ethylenedioxyphenyl, dibenzofuranyl, dibenzothiophenyl,methylenedioxyphenyl, etc.

[0109] In R, above all, aryl groups, etc. are preferred, andparticularly phenyl, etc. are preferred. R can appropriately have 1 ormore substituents.

[0110] As specific examples of the substituents, there can for examplebe mentioned

[0111] (1) substituents selected from the group consisting of azido,amino, carbamoyl, carbamoylamino, carbamoyloxy, carboxyl, cyano,sulfamoyl, sulfo, nitro, halogen, hydroxy, formyl, formylamino, cyclicsaturated C₃-C₉ aliphatic groups, cyclic unsaturated C₃-C₉ aliphaticgroups, aralkyl, N-aralkylamino, N,N-diaralkylamino, aralkyloxy,aralkylcarbonyl, N-aralkylcarbamoyl, aryl, N-arylamino, N,N-diarylamino,aryloxy, arylsulfonyl, arylsulfonyloxy, N-arylsulfonylamino,N-arylsulfonylamino C₁-C₁₀ alkylamino, N-arylsulfonylamino C₁-C₁₀alkylcarbamoyl, N-arylsulfonylamino C₁-C₆ alkoxycarbonyl, arylsulfamoyl,arylsulfamoyloxy, N-arylsulfamoyl C₁-C₁₀ alkylcarbamoyl, arylsulfamoylC₁-C₆ alkoxycarbonyl, N-arylcarbamoyl, aroyl, aroxy, N-(N-aroylamino)C₁-C₁₀ alkylcarbamoyl, N-aroylamino C₁-C₁₀ alkoxycarbonyl, C₂-C₆alkanoyl, N—C₂-C₆ alkanoylamino, N,N-di-C₂-C₆ alkanoylamino, N—C₁-C₆alkylamino, N,N-di-C₁-C₆ alkylamino, N—C₁-C₁₀ alkylcarbamoyl, N—C₁-C₁₀alkylthiocarbamoyl, N,N-di-C₁-C₁₀ alkylcarbamoyl, N,N-di-C₁-C₁₀alkylthiocarbamoyl, N—C₂-C₆ alkenylcarbamoyl, N,N-di-C₂-C₆alkenylcarbamoyl, N-amino C₁-C₁₀ alkylcarbamoyl, N—C₁-C₆ alkoxy C₁-C₁₀alkylcarbamoyl, N—C₁-C₆ alkoxycarbonyl C₁-C₁₀) alkylcarbamoyl, N—C₁-C₆alkoxycarbonylamino C₁-C₁₀ alkylcarbamoyl, N—C₁-C₆ alkoxycarbonylaminoC₁-C₆ alkoxycarbonyl, C₁-C₆ alkylthio, N—C₁-C₆ alkylsulfamoyl,N,N-di-C₁-C₆ alkylsulfamoyl, C₁-C₆ alkylsulfinyl, C₁-C₆ alkylsulfonyl,N—C₁-C₆ alkylsulfonylamino, C₁-C₆ alkoxy, C₁-C₆ alkoxycarbonyl, aminoC₁-C₆ alkoxycarbonyl, N—C₃-C₆ cycloalkylamino, N,N-di-C₃-C₆cycloalkylamino, C₃-C₆ cycloalkyloxy, N—C₃-C₆ cycloalkylcarbamoyl andN,N-di-C₃-C₆ cycloalkylcarbamoyl;

[0112] (2) 5- or 6-membered heterocyclic groups selected from the groupconsisting of the aforementioned series of groups A;

[0113] (3) monocyclic to tricyclic aromatic heterocyclic groups havingper one ring 1 to 5 hetero atoms selected from the group consisting ofnitrogen atoms, oxygen atoms and sulfur atoms, selected from the groupconsisting of the aforementioned series of groups B;

[0114] (4) substituents selected from the group consisting of N—C₁-C₁₀alkylcarbamoyl groups, N—C₁-C₁₀ alkylthiocarbamoyl groups, thiocarbonylgroups and carbonyl groups each substituted with the heterocyclic groupor the aromatic heterocyclic group; and

[0115] (5) substituents selected from the group consisting ofstraight-chain saturated C₁-C₉ aliphatic groups, straight-chainunsaturated C₁-C₉ aliphatic groups, branched saturated C₁-C₉ aliphaticgroups, branched unsaturated C₁-C₉ aliphatic groups, C₁-C₆ alkoxygroups, C₁-C₆ alkylthio groups and N—C₁-C₆ alkylamino groups each ofwhich may be substituted with the substituent,

[0116] (hereinafter, the above-mentioned groups (1) to (5) are referredto as a series of groups C).

[0117] Preferred among the substituents of R are, for example,

[0118] (1) substituents selected from the group consisting of amino,carbamoyl, carbamoylamino, carbamoyloxy, carboxyl, nitro, halogen,hydroxy, cyclic saturated C₃-C₉ aliphatic groups, cyclic unsaturatedC₃-C₉ aliphatic groups, aralkyl, N-aralkylamino, aralkyloxy,aralkylcarbonyl, N-aralkylcarbamoyl, aryl, N-arylamino, aryloxy,arylsulfonyl, arylsulfonyloxy, N-arylsulfonylamino, N-arylsulfonylaminoC₁-C₁₀ alkylamino, N-arylsulfonylamino C₁-C₁₀ alkylcarbamoyl,N-arylsulfonylamino C₁-C₆ alkoxycarbonyl, arylsulfamoyl,arylsulfamoyloxy, N-arylsulfamoyl C₁-C₁₀ alkylcarbamoyl, arylsulfamoylC₁-C₆ alkoxycarbonyl, N-arylcarbamoyl, aroyl, aroxy, N-(N-aroylamino)C₁-C₁₀ alkylcarbamoyl, N-aroylamino C₁-C₁₀ alkoxycarbonyl, C₂-C₆alkanoyl, N—C₂-C₆ alkanoylamino, N—C₁-C₆ alkylamino, N,N-di-C₁-C₆alkylamino, N—C₁-C₁₀ alkylcarbamoyl, N—C₁-C₁₀ alkylthiocarbamoyl,N,N-di-C₁-C₁₀ alkylcarbamoyl, N,N-di-C₁-C₁₀ alkylthiocarbamoyl, N—C₂-C₆alkenylcarbamoyl, N,N-di-C₂-C₆ alkenylcarbamoyl, N-amino C₁-C₁₀alkylcarbamoyl, N—C₁-C₆ alkoxy C₁-C₁₀ alkylcarbamoyl, N—C₁-C₆alkoxycarbamoyl C₁-C₁₀ alkylcarbamoyl, N—C₁-C₆ alkoxycarbonylaminoC₁-C₁₀ alkylcarbamoyl, N—C₁-C₆ alkoxycarbonylamino C₁-C₆ alkoxycarbonyl,C₁-C₆ alkylthio, C₁-C₆ alkylsulfinyl, C₁-C₆ alkylsulfonyl, N—C₁-C₆alkylsulfonylamino, C₁-C₆ alkoxy, C₁-C₆ alkoxycarbonyl, amino C₁-C₆alkoxycarbonyl, N—C₃-C₆ cycloalkylamino, N,N-di-C₃-C₆ cycloalkylamino,C₃-C₆ cycloalkyloxy, N—C₃-C₆ cycloalkylcarbamoyl and N,N-di-C3-C6cycloalkylcarbamoyl;

[0119] (2) 5- or 6-membered heterocyclic groups selected from the groupconsisting of isoxazolyl, isothiazolyl, imidazolyl, oxazolyl,oxadiazolyl, thiazolyl, thiadiazolyl, thienyl, triazolyl, pyridyl,pyrazinyl, pyrimidinyl, pyridazinyl, pyrazolyl, pyrrolyl, pyranyl,furyl, imidazolidinyl, imidazolinyl, tetrahydrofuranyl, pyrazolidinyl,pyrazolinyl, piperazinyl piperidinyl, pyrrolidinyl, pyrrolinyl andmorpholino (hereinafter, “isoxazolyl . . . and morpholino” is referredto as a series of groups A′;

[0120] (3) monocyclic to tricyclic aromatic heterocyclic groups havingper one ring 1 to 5 hetero atoms selected from the group consisting ofnitrogen atoms, oxygen atoms and sulfur atoms, selected from the groupconsisting of isoquinolyl, isoindolyl, indazolyl, indolyl,ethylenedioxyphenyl, carbazolyl, quinazolinyl, quinoxalinyl,quinolidinyl, quinolyl, cumaronyl, chromenyl, phenanthridinyl,phenanthrolinyl, dibenzofuranyl, dibenzothiophenyl,cinnolinyl,thionaphthenyl, naphthyridinyl, phenazinyl, phenoxazinyl,benzimidazolyl, benzoxazolyl, benzothiazolyl, benzotriazolyl,benzofuranyl and methylenedioxyphenyl (hereinafter, “isoquinolyl . . .and methylenedioxyphenyl” is referred to as a series of groups B′);

[0121] (4) substituents selected from the group consisting of N—C₁-C₁₀alkylcarbamoyl groups, N—C₁-C₁₀ alkylthiocarbamoyl groups, thiocarbonylgroups and carbonyl groups each substituted with the heterocyclic groupor the aromatic heterocyclic group; and

[0122] (5) substituents selected from the group consisting ofstraight-chain saturated C₁-C₉ aliphatic groups, straight-chainunsaturated C₁-C₉ aliphatic groups, branched saturated C₁-C₉ aliphaticgroups, branched unsaturated C₁-C₉ aliphatic groups, C₁-C₆ alkoxy groupsand C₁-C₆ alkylthio groups each of which may be substituted with thesubstituent,

[0123] (hereinafter, the above-mentioned groups (1) to (5) are referredto as a series of groups C′).

[0124] Particularly preferred among the substituents of R are, forexample,

[0125] (1) substituents selected from the group consisting of amino,carbamoyl, carboxyl, nitro, halogen, hydroxy, aralkylcarbonyl,N-aralkylcarbamoyl, aryl, aroyl, C₂-C₆ alkanoyl, N—C₁-C₆ alkylamino,N—C₁-C₁₀ alkylcarbamoyl, N—C₁-C₁₀ alkylthiocarbamoyl, N,N-di-C₁-C₁₀alkylcarbamoyl, N,N-di-C₁-C₁₀ alkylthiocarbamoyl, N—C₂-C₆alkenylcarbamoyl, N,N-di-C₂-C₆ alkenylcarbamoyl, N-amino C₁-C₁₀alkylcarbamoyl, N—C₁-C₆ alkoxy C₁-C₁₀ alkylcarbamoyl, N—C₁-C₆alkoxycarbonyl C₁-C₁₀ alkylcarbamoyl, C₁-C₆ alkoxy, amino C₁-C₆alkoxycarbonyl, N—C₃-C₆ cycloalkylamino, N,N-di-C₃-C₆ cycloalkylamino,C₃-C₆ cycloalkyloxy, N—C₃-C₆ cycloalkylcarbamoyl and N,N-di-C₃-C₆cycloalkylcarbamoyl;

[0126] (2) 5- or 6-membered heterocyclic groups selected from the groupconsisting of thienyl, pyridyl, pyrazinyl, pyrimidinyl, furyl,tetrahydrofuranyl and morpholino;

[0127] (3) monocyclic to tricyclic aromatic heterocyclic groups havingper one ring 1 to 5 hetero atoms selected from the group consisting ofnitrogen atoms, oxygen atoms and sulfur atoms, selected from the groupconsisting of ethylenedioxyphenyl, dibenzofuranyl, dibenzothiophenyl andmethylenedioxyphenyl;

[0128] (4) substituents selected from the group consisting of N—C₁-C₁₀alkylcarbamoyl groups, N—C₁-C₁₀ alkylthiocarbamoyl groups, thiocarbonylgroups and carbonyl groups each substituted with the heterocyclic groupor the aromatic heterocyclic group; and

[0129] (5) substituents selected from the group consisting ofstraight-chain saturated C₁-C₉ aliphatic groups, straight-chainunsaturated C₁-C₉ aliphatic groups, branched saturated C₁-C₉ aliphaticgroups, branched unsaturated C₁-C₉ aliphatic groups and C₁-C₆ alkoxygroups each of which may be substituted with the substituent(hereinafter, the above-mentioned groups (1) to (5) referred to as aseries of groups C″).

[0130] Namely, preferred as R are, for example, (1) aryl groups; (2)mono- to tricyclic C₇-C₁₅ aromatic carbocyclic groups selected from thegroup consisting of adamantyl groups, anthryl groups, indenyl groups,norbornyl groups and phenanthryl groups; (3) 5- or 6-memberedheterocyclic groups selected from the group consisting of theaforementioned series of groups A′; or (4) monocyclic to tricyclicaromatic heterocyclic groups having per one ring 1 to 5 hetero atomsselected from the group consisting of nitrogen atoms, oxygen atoms andsulfur atoms, selected from the group consisting of the aforementionedseries of groups B′, each of which groups (1) to (4) may have one ormore substituents selected from the group consisting of theaforementioned series of groups C′, and these preferred R groups arereferred to as Ra.

[0131] Particularly preferred as R are, for example, (1) aryl groups;(2) mono- to tricyclic C₇-C₁₅ aromatic carbocyclic groups selected fromthe group consisting of anthryl groups and phenanthryl groups; (3) 5- or6-membered heterocyclic groups selected from the group consisting ofthienyl, pyridyl, pyrazinyl, pyrimidinyl, furyl, tetrahydrofuranyl andmorpholino; or (4) monocyclic to tricyclic aromatic heterocyclic groupshaving per one ring 1 to 5 hetero atoms selected from the groupconsisting of nitrogen atoms, oxygen atoms and sulfur atoms, selectedfrom the group consisting of ethylenedioxyphenyl, dibenzofuranyl,dibenzothiophenyl and methylenedioxyphenyl, each of which groups (1) to(4) may have one or more substituents selected from the group consistingof the aforementioned series of groups C″, and these particularlypreferred R groups are referred to as R^(b).

[0132] R¹ and R² may be the same or different, and represent, forexample, groups selected from the group consisting of hydrogen, azido,amino, carbamoyl, carbamoylamino, carbamoyloxy, carboxyl, cyano,sulfamoyl, sulfo, nitro, halogen, hydroxy, formyl, formylamino, cyclicsaturated C₃-C₉ aliphatic groups, cyclic unsaturated C₃-C₉ aliphaticgroups, aralkyl, N-aralkylamino, aralkyloxy, aralkylcarbonyl, aryl,N-arylamino, aryloxy, arylsulfonyl, N-arylsulfonylamino,N-arylsulfonylamino C₁-C₁₀ alkylamino, N-arylsulfonylamino C₁-C₁₀alkylcarbamoyl, N-arylsulfonylamino C₁-C₆ alkoxycarbonyl, C₂-C₆alkanoyl, N—C₂-C₆ alkanoylamino, aroyl, N-aroylamino, N-aroyl C₁-C₁₀alkylamino, N-aroyl C₁-C₁₀ alkylcarbamoyl, N—C₁-C₆ alkylamino,N,N-di-C₁-C₆ alkylamino, N—C₁-C₁₀ alkylcarbamoyl, N,N-di-C₁-C₁₀alkylcarbamoyl, N—C₁-C₆ alkylsulfamoyl, C₁-C₆ alkylsulfinyl, C₁-C₆alkylsulfonyl, N—C₁-C₆ alkylsulfonylamino, C₁-C₆ alkylthio, C₁-C₆alkoxy, C₁-C₆ alkoxycarbonyl, N—C₃-C₆ cycloalkylamino, C₃-C₆cycloalkyloxy and N—C₃-C₆ cycloalkylcarbamoyl (hereinafter, “hydrogen, .. . and N—C₃-C₆ cycloalkylcarbamoyl” is referred to as a series ofgroups D); or straight-chain saturated C₁-C₉ aliphatic groups,straight-chain unsaturated C₁-C₉ aliphatic groups, branched saturatedC₁-C₉ aliphatic groups or branched unsaturated C₁-C₉ aliphatic groups,N—C₁-C₆ alkylamino groups, C₁-C₆ alkylthio groups or C₁-C₆ alkoxy groupseach of which may optionally be substituted with the above group.

[0133] Preferred as R¹ and R² are, for example, groups selected from thegroup consisting of hydrogen, amino, carboxyl, cyano, sulfamoyl, sulfo,nitro, halogen, hydroxy, formyl, cyclic saturated C₃-C₉ aliphaticgroups, cyclic unsaturated C₃-C₉ aliphatic groups, aralkyl, aryl,N-arylamino, aryloxy, C₂-C₆ alkanoyl, N—C₂-C₆ alkanoylamino, aroyl,N-C₁-C₆ alkylamino, N,N-di-C₁-C₆ alkylamino, N—C₁-C₁₀ alkylcarbamoyl,N—C₁-C₆ alkylsulfamoyl, C₁-C₆ alkylsulfinyl, C₁-C₆ alkylsulfonyl,N—C₁-C₆ alkylsulfonylamino, C₁-C₆ alkoxy, C₁-C₆ alkoxycarbonyl, N—C₃-C₆cycloalkylamino, C₃-C₆ cycloalkyloxy and N—C₃-C₆ cycloalkylcarbamoyl(hereinafter, “hydrogen, . . . and N—C₃-C₆ cycloalkylcarbamoyl” isreferred to as a series of groups D′); or straight-chain saturated C₁-C₉aliphatic groups, straight-chain unsaturated C₁-C₉ aliphatic groups,branched saturated C₁-C₉ aliphatic groups, branched unsaturated C₁-C₉aliphatic groups or C₁-C₆ alkoxy groups each of which may optionally besubstituted with the above group.

[0134] Particularly preferred as R¹ and R² are, for example, groupsselected from the group consisting of hydrogen, amino, nitro, halogen,hydroxy, aryl, N-arylamino, N—C₁-C₆ alkylamino, N,N-di-C₁-C₆ alkylamino,N—C₁-C₁₀ alkylcarbamoyl, C₁-C₆ alkoxy, C₁-C₆ alkoxycarbonyl and N—C₃-C₆cycloalkylamino; or straight-chain saturated C₁-C₉ aliphatic groups,straight-chain unsaturated C₁-C₉ aliphatic groups, branched saturatedC₁-C₉ aliphatic groups, branched unsaturated C₁-C₉ aliphatic groups orC₁-C₆ alkoxy groups each of which may optionally be substituted with theabove group.

[0135] R³ and R⁴ may be the same or ditterent, and represent

[0136] (1) for example, groups selected from the group consisting ofhydrogen, azido, amidino, amino, carbamoyl, carbamoylamino,carbamoyloxy, carboxyl, guanidino, cyano, sulfamoyl, sulfo, nitro,halogen, hydroxy, formyl, formylamino, cyclic saturated C₃-C₉ aliphaticgroups, cyclic unsaturated C₃-C₉ aliphatic groups, C₂-C₆ alkanoyl,N-C₂-C₆ alkanoylamino, N—C₁-C₆ alkylamino, N,N-di-C₁-C₆ alkylamino,N—C₁-C₁₀ alkylcarbamoyl, N,N-di-C₁-C₁₀ alkylcarbamoyl, C₁-C₆ alkylthio,N—C₁-C₆ alkylsulfamoyl, C₁-C₆ alkylsulfinyl, C₁-C₆ alkylsulfonyl,N—C₁-C₆ alkylsulfonylamino, C₁-C₆ alkoxy, C₁-C₆ alkoxycarbonyl, N—C₃-C₆cycloalkylamino, C₃-C₆ cycloalkyloxy and N—C₃-C₆ cycloalkylcarbamoyl(hereinafter, “hydrogen, . . . and N—C₃-C₆ cycloalkylcarbamoyl” isreferred to as a series of groups E),

[0137] (2) for example, groups selected from the group consisting ofstraight-chain saturated C₁-C₉ aliphatic groups, straight-chainunsaturated C₁-C₉ aliphatic groups. branched saturated C₁-C₉ aliphaticgroups and branched unsaturated C₁-C₉ aliphatic groups, each of whichmay optionally be substituted with the above-mentioned group, or

[0138] (3) for example, aryl groups; monocyclic to tricyclic C₇-C₁₅aromatic carbocyclic groups selected from the group consisting ofacenaphthylenyl, adamantyl, anthryl, indenyl, norbornyl and phenanthryl;5- or 6-membered heterocyclic groups selected from the group consistingof isoxazolyl, isothiazolyl, imidazolyl, oxazolyl, oxadiazolyl,thiazolyl, thiadiazolyl, thienyl, triazinyl, triazolyl, pyridyl,pyrazinyl, pyrimidinyl, pyridazinyl, pyrazolyl, pyrrolyl, pyranyl,furyl, furazanyl, imidazolidinyl, imidazolinyl, tetrahydrofuranyl,pyrazolidinyl, pyrazolinyl, piperazinyl, piperidinyl, pyrrolidinyl,pyrrolinyl and morpholino; monocyclic to tricyclic aromatic heterocyclicgroups having per one ring 1 to 5 hetero atoms selected from the groupconsisting of nitrogen atoms, oxygen atoms and sulfur atoms, selectedfrom the group consisting of the aforementioned series of groups B; orstraight-chain saturated C₁-C₉ aliphatic groups, straight-chainunsaturated C₁-C₉ aliphatic groups, branched saturated C₁-C₉ aliphaticgroups or branched unsaturated C₁-C₉ aliphatic groups, each of whichgroups may be substituted with the aryl group, the aromatic carbocyclicgroup, the heterocyclic group or the aromatic heterocyclic group, or

[0139] (4) R³ and R⁴ combine together to form a straight-chain saturatedC₁-C₉ aliphatic group, a straight-chain unsaturated C₁-C₉ aliphaticgroup, a branched saturated C₁-C₉ aliphatic group, a branchedunsaturated C₁-C₉ aliphatic group, a 5- or 6-membered saturatedcarbocyclic group or a 5- or 6-membered unsaturated carbocyclic group.

[0140] When embodiments of R³ and R⁴ are specifically described, aspreferred groups in (1), there can for example be mentioned groupsselected from the group consisting of hydrogen, azido, amidino, amino,carbamoyl, carbamoylamino, carbamoyloxy, carboxyl, guanidino, cyano,sulfamoyl, sulfo, nitro, halogen, hydroxy, formyl, formylamino, cyclicsaturated C₃-C₉ aliphatic groups, cyclic unsaturated C₃-C₉ aliphaticgroups, C₂-C₆ alkanoyl, N—C₁-C₆ alkylamino, N—C₁-C₁₀ alkylcarbamoyl,C₁-C₆ alkylthio, N—C₁-C₆ alkylsulfamoyl, C₁-C₆ alkylsulfinyl, C₁-C₆alkylsulfonyl, N—C₁-C₆ alkylsulfonylamino, C₁-C₆ alkoxy, C₁-C₆alkoxycarbonyl and N—C₃-C₆ cycloalkylamino (hereinafter, “hydrogen . . .and N—C₃-C₆ cycloalkylamino” is referred to as a series of groups E′),and particularly preferred among them are for example hydrogen, azido,amidino, amino, carbamoyl, carboxyl, guanidino, cyano, sulfamoyl, sulfo,nitro, halogen, hydroxy, formyl, cyclic saturated C₃-C₉ aliphaticgroups, cyclic unsaturated C₃-C₉ aliphatic groups, N—C₁-C₆ alkylamino,N—C₁-C₁₀ alkylcarbamoyl, C₁-C₆ alkylthio, C₁-C₆ alkoxy and C₁-C₆alkoxycarbonyl (hereinafter, “hydrogen, . . . and C₁-C₆ alkoxycarbonyl”is referred to as a series of groups E″),

[0141] As preferred groups in (2), there can for example be mentionedgroups selected from the group consisting of straight-chain saturatedC₁-C₉ aliphatic groups, straight-chain unsaturated C₁-C₉ aliphaticgroups, branched saturated C₁-C₉ aliphatic groups and branchedunsaturated C₁-C₉ aliphatic groups, each of which groups may besubstituted with the group referred to in the immediately above (1),namely a group selected from the group consisting of the above-mentionedseries of groups E′, especially the above-mentioned series of groups E″.

[0142] As preferred groups in (3), there can for example be mentionedaryl groups; mono- to tricyclic C₇-C₁₅ aromatic carbocyclic groupsselected from the group consisting of adamantyl, anthryl, indenyl,norbornyl and phenanthryl; 5- or 6-membered heterocyclic groups selectedfrom the group consisting of the aforementioned series of groups A′;monocyclic to tricyclic aromatic heterocyclic groups having per one ring1 to 5 hetero atoms selected from the group consisting of nitrogenatoms, oxygen atoms and sulfur atoms, selected from the group consistingof the aforementioned series of groups B′; and straight-chain saturatedC₁-C₉ aliphatic groups, straight-chain unsaturated C₁-C₉ aliphaticgroups, branched saturated C₁-C₉ aliphatic groups or branchedunsaturated C₁-C₉ aliphatic groups, each of which may be substitutedwith the aryl group, the aromatic carbocyclic group, the heterocyclicgroup or the aromatic heterocyclic group.

[0143] Particularly preferred as the groups in (3) are for example arylgroups; mono- to tricyclic C₇-C₁₅ aromatic carbocyclic groups selectedfrom the group consisting of anthryl and phenanthryl; 5- or 6-memberedheterocyclic groups selected from the group consisting of thienyl,pyridyl, pyrazinyl, pyrimidinyl, furyl, tetrahydrofuranyl andmorpholino; monocyclic to tricyclic aromatic heterocyclic groups havingper one ring 1 to 5 hetero atoms selected from the group consisting ofnitrogen atoms, oxygen atoms and sulfur atoms, selected from the groupconsisting of ethylenedioxyphenyl, dibenzofuranyl, dibenzothiophenyl andmethylenedioxyphenyl; and straight-chain saturated C₁-C₉ aliphaticgroups, straight-chain unsaturated C₁-C₉ aliphatic groups, branchedsaturated C₁-C₉ aliphatic groups or branched unsaturated C₁-C₉ aliphaticgroups, each of which may be substituted with the aryl group, thearomatic carbocyclic group, the heterocyclic group or the aromaticheterocyclic group.

[0144] In (3), the aryl groups; the mono- to tricyclic C₇-C₁₅ aromaticcarbocyclic groups; the 5- or 6-membered heterocyclic groups; themonocyclic to tricyclic aromatic heterocyclic groups having per one ring1 to 5 hetero atoms selected from the group consisting of nitrogenatoms, oxygen atoms and sulfur atoms; and the straight-chain saturatedC₁-C₉ aliphatic groups, straight-chain unsaturated C₁-C₉ aliphaticgroups, branched saturated C₁-C₉ aliphatic groups or branchedunsaturated C₁-C₉ aliphatic groups each of the groups being optionallysubstituted with the aryl group, the aromatic carbocyclic group, theheterocyclic group or the aromatic heterocyclic groups, may have one ormore substituents. As the substituents, the same substituents as thosewhich R may have can be mentioned.

[0145] As preferred embodiments in (4), there can be mentioned the casewhere R³ and R⁴ combine together to form a straight-chain saturatedC₁-C₉ aliphatic group, a straight-chain unsaturated C₁-C₉ aliphaticgroup, a branched saturated C₁-C₉ aliphatic group, a branchedunsaturated C₁-C₉ aliphatic group, a 5- or 6-membered saturatedcarbocyclic group, or a 5- or 6-membered unsaturated carbocyclic group,and preferred among them is the case where a straight-chain unsaturatedC₁-C₉ aliphatic group or a 5- or 6-membered saturated carbocyclic groupis formed.

[0146] Therefore, preferably, R³ and R⁴ are the same or different andrepresent

[0147] (1a) groups selected from the group consisting of theaforementioned series of groups E′,

[0148] (2a) straight-chain saturated C₁-C₉ aliphatic groups,straight-chain unsaturated C₁-C₉ aliphatic groups, branched saturatedC₁-C₉ aliphatic groups or branched unsaturated C₁-C₉ aliphatic groups,each of which groups may be substituted with the above group, or

[0149] (3a) (3a-1) aryl groups; (3a-2) mono- to tricyclic C₇-C₁₅aromatic carbocyclic group selected from the group consisting ofadamantyl, anthryl, indenyl, norbornyl and phenanthryl; (3a-3) 5- or6-membered heterocyclic groups selected from the group consisting of theaforementioned series of groups A′; (3a-4) monocyclic to tricyclicaromatic heterocyclic groups having per one ring 1 to 5 hetero atomsselected from the group consisting of nitrogen atoms, oxygen atoms andsulfur atoms, selected from the group consisting of the aforementionedseries of groups B′; or (3a-5) straight-chain saturated C₁-C₉ aliphaticgroups, straight-chain unsaturated C₁-C₉ aliphatic groups, branchedsaturated C₁-C₉ aliphatic groups or branched unsaturated C₁-C₉ aliphaticgroups, each of which groups may be substituted with the above-mentionedaryl group, aromatic carbocyclic group, heterocyclic group or aromaticheterocyclic group;

[0150] each of the above-mentioned groups (3a-1) to (3a-5) beingoptionally substituted with one or more substituents selected from thegroup consisting of the aforementioned series of groups C′, or

[0151] (4a) R³ and R⁴ combine together to form a straight-chainsaturated C₁-C₉ aliphatic group, a straight-chain unsaturated C₁-C₉aliphatic group, a branched saturated C₁-C₉ aliphatic group or abranched unsaturated C₁-C₉ aliphatic group, a 5- or 6-membered saturatedcarbocyclic group, or a 5- or 6-membered unsaturated carbocyclic group,and these preferred R³ and R⁴ groups are referred to as R^(3a) andR^(4a).

[0152] Particularly preferably, R³ and R⁴ are the same or different, andrepresent

[0153] (1b) groups selected from the group consisting of theaforementioned series of groups E″,

[0154] (2b) groups selected from the group consisting of straight-chainsaturated C₁-C₉ aliphatic groups, straight-chain unsaturated C₁-C₉aliphatic groups, branched saturated C₁-C₉ aliphatic groups and branchedunsaturated C₁-C₉ aliphatic groups, each of which groups may besubstituted with the above-mentioned group, or

[0155] (3b) (3b-1) aryl groups; (3b-2) mono- to tricyclic C₇-C₁₅aromatic carbocyclic group selected from the group consisting of anthryland phenanthryl; (3b-3) 5- or 6-membered heterocyclic groups selectedfrom the group consisting of thienyl, pyridyl, pyrazinyl, pyrimidinyl,furyl, tetrahydrofuranyl and morpholino; (3b-4) monocyclic to tricyclicaromatic heterocyclic groups having per one ring 1 to 5 hetero atomsselected from the group consisting of nitrogen atoms, oxygen atoms andsulfur atoms, selected from the group consisting of ethylenedioxyphenyl,dibenzofuranyl, dibenzothiophenyl and methylenedioxyphenyl; or (3b-5)straight-chain saturated C₁-C₉ aliphatic groups, straight-chainunsaturated C₁-C₉ aliphatic groups, branched saturated C₁-C₉ aliphaticgroups or branched unsaturated C₁-C₉ aliphatic groups, each of whichgroups may be substituted with the above-mentioned aryl group, aromaticcarbocyclic group, heterocyclic group or aromatic heterocyclic group;

[0156] each of the above-mentioned groups (3b-1) to (3b-5) beingoptionally substituted with one or more substituents selected from thegroup consisting of the aforementioned series of groups C″, or

[0157] (4b) R³ and R⁴ combine together to form a straight-chainunsaturated C₁-C₉ aliphatic group or a 5- or 6-membered saturatedcarbocyclic group, and these particularly preferred R³ and R⁴ groups arereferred to as R^(3b) and R^(4b).

[0158] X₁ represents for example an oxygen atom, a sulfur atom or agroup NR⁵ (wherein R⁵ represents a group selected from the groupconsisting of hydrogen, halogen, hydroxy, N—C₁-C₆ alkylsulfonylamino,C₁-C₆ alkoxy, C₁-C₆ alkoxycarbonyl, C₂-C₆ alkanoyl, carbamoyl andN—C₁-C₁₀ alkylcarbamoyl; or a straight-chain saturated C₁-C₉ aliphaticgroup, a straight-chain unsaturated C₁-C₉ aliphatic group, a branchedsaturated C₁-C₉ aliphatic group or a branched unsaturated C₁-C₉aliphatic group, each of which groups may be substituted with theabove-mentioned group).

[0159] Preferred as X₁ among them is an oxygen atom, a sulfur atom or agroup NR^(5a) (wherein R^(5a) represents a group selected from the groupconsisting of hydrogen, halogen, hydroxy, N—C₁-C₆ alkylsulfonylamino,C₁-C₆ alkoxy, C₁-C₆ alkoxycarbonyl, C₂-C₆ alkanoyl, carbamoyl andN—C₁-C₁₀ alkylcarbamoyl; or a straight-chain saturated C₁-C₉ aliphaticgroup, a straight-chain unsaturated C₁-C₉ aliphatic group, a branchedsaturated C₁-C₉ aliphatic group or a branched unsaturated C₁-C₉aliphatic group, each of which groups may be substituted with theabove-mentioned group).

[0160] Particularly preferred as X₁ among them is an oxygen atom or agroup NR^(5b) (wherein R^(5b) represents a group selected from the groupconsisting of hydrogen, hydroxy, C₁-C₆ alkoxy, C₁-C₆ alkoxycarbonyl andN—C₁-C₁₀ alkylcarbamoyl; or a straight-chain saturated C₁-C₉ aliphaticgroup, a straight-chain unsaturated C₁-C₉ aliphatic group, a branchedsaturated C₁-C₉ aliphatic group or a branched unsaturated C₁-C₉aliphatic group, each of which groups may be substituted with theabove-mentioned group).

[0161] X₂ represents for example an oxygen atom or a sulfur atom.

[0162] Y represents for example an oxygen atom, a sulfur atom, a groupNR⁵ or a group CR⁶R⁷ (wherein R⁶ is a group selected from the groupconsisting of hydrogen, halogen, hydroxy, N—C₁-C₆ alkylsulfonylamino,C₁-C₆ alkoxy, C₁-C₆ alkoxycarbonyl, C₂-C₆ alkanoyl, carbamoyl andN—C₁-C₁₀ alkylcarbamoyl; or a straight-chain saturated C₁-C₉ aliphaticgroup, a straight-chain unsaturated C₁-C₉ aliphatic group, a branchedsaturated C₁-C₉ aliphatic group or a branched unsaturated C₁-C₉aliphatic group, each of which groups may be substituted with theabove-mentioned group, R⁷ represents hydrogen or C₁-C₆ alkyl, and R⁵ isas defined above).

[0163] Preferred as Y among them is an oxygen atom, a sulfur atom, agroup NR^(5a) or a group CR^(6a)R^(7a) (wherein R^(6a) is a groupselected from the group consisting of hydrogen, halogen, hydroxy,N—C₁-C₆ alkylsulfonylamino, C₁-C₆ alkoxy, C₁-C₆ alkoxycarbonyl, C₂-C₆alkanoyl, carbamoyl and N—C₁-C₁₀ alkylcarbamoyl; or a straight-chainsaturated C₁-C₉ aliphatic group, a straight-chain unsaturated C₁-C₉aliphatic group, a branched saturated C₁-C₉ aliphatic group or abranched unsaturated C₁-C₉ aliphatic group, each of which groups may besubstituted with the above-mentioned group, R^(7a) represents hydrogenor C₁-C₆ alkyl, and R^(5a) is as defined above).

[0164] Particularly preferred as Y among them is an oxygen atom, asulfur atom or a group CR^(6b)R^(7b) (wherein R^(6b) is a group selectedfrom the group consisting of hydrogen, hydroxy, C₁-C₆ alkoxy, C₁-C₆alkoxycarbonyl and N—C₁-C₁₀ alkylcarbamoyl; or a straight-chainsaturated C₁-C₉ aliphatic group, a straight-chain unsaturated C₁-C₉aliphatic group, a branched saturated C₁-C₉ aliphatic group or abranched unsaturated C₁-C₉ aliphatic group, each of which groups may besubstituted with the above-mentioned group, and R^(7b) representshydrogen or C₁-C₆ alkyl)

[0165] Z represents for example a bi- or tricyclic saturated orunsaturated C₆-C₁₅ condensed carbocyclic group selected from the groupconsisting of condensed aryl, acenaphthylenyl, adamantyl, anthryl,indanyl, indenyl, C₆-C₈ cycloalkanyl, C₆-C₈ cycloalkadienyl, C₆-C₈cycloalkenyl, norbornyl, phenanthryl and fluorenyl; a 6-memberedheterocyclic group selected from the group consisting of isoquinolyl,isoindolyl, indazolyl, indolyl, indolizinyl, ethylenedioxyphenyl,quinazolinyl, quinoxalinyl, quinolidinyl, quinolyl, cumaronyl,chromenyl, thionaphthenyl, naphthyridinyl, pyridyl, pyrazinyl,pyrimidinyl, pyridazinyt, pyranyl, phthalazinyl, benzimidazolyl,benzoxazolyl, benzothiazolyl, benzotriazolyl, benzofuranyl andmethylenedioxyphenyl; or a bi- or tricyclic condensed aromaticheterocyclic group having per one ring 1 to 5 hetero atoms selected fromthe group consisting of nitrogen atoms, oxygen atoms and sulfur atoms.

[0166] Preferred as Z among them is a bi- or tricyclic saturated orunsaturated C₆-C₁₅ condensed carbocyclic group selected from the groupconsisting of condensed aryl, adamantyl, anthryl, indanyl, indenyl,C₆-C₈ cycloalkanyl, C₆-C₈ cycloalkadienyl, C₆-C₈ cycloalkenyl, norbornyland phenanthryl; a 6-membered heterocyclic group selected from the groupconsisting of ethylenedioxyphenyl, pyridyl, pyrazinyl, pyrimidinyl,pyridazinyl, benzimidazolyl, benzoxazolyl, benzothiazolyl,benzotriazolyl, benzofuranyl and methylenedioxyphenyl; or a bi- ortricyclic condensed aromatic heterocyclic group having per one ring 1 to5 hetero atoms selected from the group consisting of nitrogen atoms,oxygen atoms and sulfur atoms.

[0167] Particularly preferred as Z among them is a bi- or tricyclicsaturated or unsaturated C₆-C₁₅ condensed carbocyclic group selectedfrom the group consisting of condensed aryl, anthryl, C₆-C₈cycloalkanyl, C₆-C₈ cycloalkadienyl and C₆-C₈ cycloalkenyl; a 6-memberedheterocyclic group selected from the group consisting ofethylenedioxyphenyl, pyridyl, pyrazinyl, pyrimidinyl, pyridazinyl andmethylenedioxyphenyl; or a bi- or tricyclic condensed aromaticheterocyclic group having per one ring 1 to 5 hetero atoms selected fromthe group consisting of nitrogen atoms, oxygen atoms and sulfur atoms.

[0168] Next, description is made on the compounds of the general formula[I] of the invention.

[0169] Among compounds represented by the general formula [I]

[0170] (wherein R, R¹, R², R³, R⁴, X₁, X₂, Y and Z are as defined above), preferred are compounds represented by the general formula [I-a]

[0171] [wherein,

[0172] R^(a) represents (1) an aryl group; (2) a mono- to tricyclicC₇-C₁₅ aromatic carbocyclic group selected from the group consisting ofadamantyl, anthryl, indenyl, norbornyl and phenanthryl; (3) a 5- or6-membered heterocyclic group selected from the group consisting of theaforementioned series of groups A′; or (4) a monocyclic to tricyclicaromatic heterocyclic group having per one ring 1 to 5 hetero atomsselected from the group consisting of nitrogen atoms, oxygen atoms andsulfur atoms, selected from the group consisting of the aforementionedseries of groups B′, each of which groups (1) to (4) may have assubstituents one or more groups selected from the group consisting ofgroups selected from the group consisting of the aforementioned seriesof groups C′,

[0173] R^(1a) and R^(2a) are the same or different, and represent groupsselected from the group consisting of the aforementioned series ofgroups D′; or straight-chain saturated C₁-C₉ aliphatic groups,straight-chain unsaturated C₁-C₉ aliphatic groups, branched saturatedC₁-C₉ aliphatic groups, branched unsaturated C₁-C₉ aliphatic groups, orC₁-C₆ alkoxy groups, each of which groups may optionally be substitutedwith the above-mentioned group,

[0174] R^(3a) and R^(4a) are the same or different, and represent

[0175] (1) groups selected from the group consisting of theaforementioned series of groups E′,

[0176] (2) groups selected from the group consisting of straight-chainsaturated C₁-C₉ aliphatic groups, straight-chain unsaturated C₁-C₉aliphatic groups, branched saturated C₁-C₉ aliphatic groups, andbranched unsaturated C₁-C₉ aliphatic groups, each of which groups mayoptionally be substituted with the above-mentioned group, or

[0177] (3) (3-1) aryl groups; (3-2) mono- to tricyclic C₇-C₁₅ aromaticcarbocyclic groups selected from the group consisting of adamantyl,anthryl, indenyl, norbornyl and phenanthryl; (3-3) 5- or 6-memberedheterocyclic groups selected from the group consisting of theaforementioned series of groups A′; (3-4) monocyclic to tricyclicaromatic heterocyclic groups having per one ring 1 to 5 hetero atomsselected from the group consisting of nitrogen atoms, oxygen atoms andsulfur atoms, selected from the group consisting of the aforementionedseries of groups B′; or (3-5) straight-chain saturated C₁-C₉ aliphaticgroups, straight-chain unsaturated C₁-C₉ aliphatic groups, branchedsaturated C₁-C₉ aliphatic groups or branched unsaturated C₁-C₉ aliphaticgroups, each of which groups may be substituted with the above-mentionedaryl group; aromatic carbocyclic group, heterocyclic group or aromaticheterocyclic group;

[0178] each of which groups (3-1) to (3-5) may optionally have one ormore substituents selected from the group consisting of theaforementioned series of groups C′, or

[0179] (4) R^(3a) and R^(4a) combine together to form straight-chainsaturated C₁-C₉ aliphatic groups, straight-chain unsaturated C₁-C₉aliphatic groups, branched saturated C₁-C₉ aliphatic groups, branchedunsaturated C₁-C₉ aliphatic groups, 5- or 6-membered saturatedcarbocyclic groups, or 5- or 6-membered unsaturated carbocyclic groups,

[0180] X_(1a) represents an oxygen atom, a sulfur atom, or a groupNR^(5a) (wherein R^(5a) represents a group selected from the groupconsisting of hydrogen, halogen, hydroxy, N—C₁-C₆ alkylsulfonylamino,C₁-C₆ alkoxy, C₁-C₆ alkoxycarbonyl, C₂-C₆ alkanoyl, carbamoyl andN—C₁-C₁₀ alkylcarbamoyl; or a straight-chain saturated C₁-C₉ aliphaticgroup, a straight-chain unsaturated C₁-C₉ aliphatic group, a branchedsaturated C₁-C₉ aliphatic group or a branched unsaturated C₁-C₉aliphatic group, each of which groups may be substituted with theabove-mentioned group),

[0181] X_(2a) represents an oxygen atom or a sulfur atom,

[0182] Y_(a) represents an oxygen atom, a sulfur atom, a group NR^(5a)or a group CR^(6a)R^(7a) (wherein R^(6a) is a group selected from thegroup consisting of hydrogen, halogen, hydroxy, N—C₁-C₆alkylsulfonylamino, C₁-C₆ alkoxy, C₁-C₆ alkoxycarbonyl, C₂-C₆ alkanoyl,carbamoyl and N—C₁-C₁₀ alkylcarbamoyl; or a straight-chain saturatedC₁-C₉ aliphatic group, a straight-chain unsaturated C₁-C₉ aliphaticgroup, a branched saturated C₁-C₉ aliphatic group or a branchedunsaturated C₁-C₉ aliphatic group, each of which groups may besubstituted with the above-mentioned group, R^(7a) represents hydrogenor C₁-C₆ alkyl, and R^(5a) is as defined above), and

[0183] Z_(a) represents a bi- or tricyclic saturated or unsaturatedC₆-C₁₅ condensed carbocyclic group selected- from the group consistingof condensed aryl, adamantyl, anthryl, indanyl, indenyl, C₆-C₈cycloalkanyl, C₆-C₈ cycloalkadienyl, C₆-C₈ cycloalkenyl, norbornyl andphenanthryl; a 6-membered heterocyclic group selected from the groupconsisting of ethylenedioxyphenyl, pyridyl, pyrazinyl, pyrimidinyl,pyridazinyl, benzimidazolyl, benzoxazolyl, benzothiazolyl,benzotriazolyl, benzofuranyl and methylenedioxyphenyl; or a bi- ortricyclic condensed aromatic heterocyclic group having per one ring 1 to5 hetero atoms selected from the group consisting of nitrogen atoms,oxygen atoms and sulfur atoms].

[0184] Among compounds represented by the general formula [I],particularly preferred are compounds represented by the general formula[1-b]

[0185] [wherein,

[0186] R_(b) represents (1) an aryl group; (2) a mono- to tricyclicC₇-C₁₅ aromatic carbocyclic group selected from the group consisting ofanthryl and phenanthryl; (3) a 5- or 6-membered heterocyclic groupselected from the group consisting of thienyl, pyridyl, pyrazinyl,pyrimidinyl, furyl, tetrahydrofuranyl and morpholino; or (4) amonocyclic to tricyclic aromatic heterocyclic group having per one ring1 to 5 hetero atoms selected from the group consisting of nitrogenatoms, oxygen atoms and sulfur atoms, selected from the group consistingof ethylenedioxyphenyl, dibenzofuranyl, dibenzothiophenyl andmethylenedioxyphenyl,

[0187] each of which groups (1) to (4) may have one or more substituentsselected from the group consisting of the aforementioned series ofgroups C″,

[0188] R^(1b) and R^(2b) are the same or different, and representsubstituents selected from the group consisting of hydrogen, amino,nitro, halogen, hydroxy, aryl, N-arylamino, N-C₁-C₆ alkylamino,N,N-di-C₁-C₆ alkylamino, N—C₁-C₁₀ alkylcarbamoyl, C₁-C₆ alkoxy, C₁-C₆alkoxycarbonyl and N—C₃-C₆ cycloalkylamino; or straight-chain saturatedC₁-C₉ aliphatic groups, straight-chain unsaturated C₁-C₉ aliphaticgroups, branched saturated C₁-C₉ aliphatic groups or branchedunsaturated C₁-C₉ aliphatic groups, or C₁-C₆ alkoxy groups, each ofwhich groups may be substituted with the above group,

[0189] R^(3b) and R^(4b) are the same or different, and represent

[0190] (1) groups selected from the group consisting of hydrogen; azido,amidino, amino, carbamoyl, carboxyl, guanidino, cyano, sulfamoyl, sulfo,nitro, halogen, hydroxy, formyl, cyclic saturated C₃-C₉ aliphaticgroups, cyclic unsaturated C₃-C₉ aliphatic groups, N—C₁-C₆ alkylamino,N—C₁-C₁₀ alkylcarbamoyl, C₁-C₆ alkylthio, C₁-C₆ alkoxy and C₁-C₆alkoxycarbonyl,

[0191] (2) groups selected from the group consisting of straight-chainsaturated C₁-C₉ aliphatic groups, straight-chain unsaturated C₁-C₉aliphatic groups, branched saturated C₁-C₉ aliphatic groups and branchedunsaturated C₁-C₉ aliphatic groups, each of which groups may besubstituted with the above group, or

[0192] (3) (3-1) aryl groups; (3-2) mono- to tricyclic C₇-C₁₅ aromaticcarbocyclic groups selected from the group consisting of anthryl andphenanthryl; (3-3) 5- or 6-membered heterocyclic groups selected fromthe group consisting of thienyl, pyridyl, pyrazinyl, pyrimidinyl, furyl,tetrahydrofuranyl and morpholino; (3-4) monocyclic to tricyclic aromaticheterocyclic groups having per one ring 1 to 5 hetero atoms selectedfrom the group consisting of nitrogen atoms, oxygen atoms and sulfuratoms, selected from the group consisting of ethylenedioxyphenyl,dibenzofuranyl, dibenzothiophenyl and methylenedioxyphenyl; or (3-5)straight-chain saturated C₁-C₉ aliphatic groups, straight-chainunsaturated C₁-C₉ aliphatic groups, branched saturated C₁-C₉ aliphaticgroups or branched unsaturated C₁-C₉ aliphatic groups, each of whichgroups may be substituted with the above-mentioned aryl group, aromaticcarbocyclic group, heterocyclic group or aromatic heterocyclic group;

[0193] each of which groups (3-1) to (3-5) may optionally have one ormore substituents selected from the group consisting of theaforementioned series of groups C″, or

[0194] (4) R^(3b) and R^(4b) combine together to form a straight-chainunsaturated C₁-C₉ aliphatic group or a 5- or 6-membered saturatedcarbocyclic group,

[0195] X_(1b) represents an oxygen atom, or a group NR^(5b) (whereinR^(5b) represents a group selected from the group consisting ofhydrogen, hydroxy, C₁-C₆ alkoxy, C₁-C₆ alkoxycarbonyl and N—C₁-C₁₀alkylcarbamoyl; or a straight-chain saturated C₁-C₉ aliphatic group, astraight-chain unsaturated C₁-C₉ aliphatic group, a branched saturatedC₁-C₉ aliphatic group or a branched unsaturated C₁-C₉ aliphatic group,each of which groups may be substituted with the above-mentioned group),

[0196] X_(2b) represents an oxygen atom or a sulfur atom,

[0197] Y_(b) represents an oxygen atom, a sulfur atom or a groupCR^(6b)R^(7b) (wherein R^(6b) is a group selected from the groupconsisting of hydrogen, hydroxy, C₁-C₆ alkoxy, C₁-C₆ alkoxycarbonyl andN—C₁-C₁₀ alkylcarbamoyl; or a straight-chain saturated C₁-C₉ aliphaticgroup, a straight-chain unsaturated C₁-C₉ aliphatic group, a branchedsaturated C₁-C₉ aliphatic group or a branched unsaturated C₁-C₉aliphatic group, each of which groups may be substituted with theabove-mentioned group, and R^(7b) represents hydrogen or C₁-C₆ alkyl),and

[0198] Z_(b) represents a bi- or tricyclic saturated or unsaturatedC₆-C₁₅ condensed carbocyclic group selected from the group consisting ofcondensed aryl, anthryl, C₆-C₈ cycloalkanyl, C₆-C₈ cycloalkadienyl andC₆-C₈ cycloalkenyl; a 6-membered heterocyclic group selected from thegroup consisting of ethylenedioxyphenyl, pyridyl, pyrazinyl,pyrimidinyl, pyridazinyl and methylenedioxyphenyl; or a bi- or tricycliccondensed aromatic heterocyclic group having per one ring 1 to 5 heteroatoms selected from the group consisting of nitrogen atoms, oxygen atomsand sulfur atoms].

[0199] Further, compounds represented by the following general formula[I-c] are compounds disclosed in base application for the priority ofthe present application, and are included in the compounds of thegeneral formula [I] of the invention.

[0200] [wherein,

[0201] R^(c) represents an aryl group, a mono- to tricyclic C₇-C₁₅aromatic carbocyclic group (provided that an aryl group is excluded), a5- or 6-membered heterocyclic group, or a monocyclic to tricyclicaromatic heterocyclic groups having per one ring 1 to 5 hetero atomsselected from the group consisting of nitrogen atoms, oxygen atoms andsulfur atoms (provided that a 5- or 6-membered heterocyclic group isexcluded), R^(1c) and R^(2c) are the same or different, and representgroups selected from the group consisting of hydrogen, azido, amino,carbamoyl, carbamoylamino, carbamoyloxy, carboxyl, cyano, sulfamoyl,sulfo, nitro, halogen, hydroxy, formyl, formylamino, cyclic saturated orunsaturated C₃-C₉ aliphatic groups, aralkyl, N-aralkylamino, aralkyloxy,aralkylcarbonyl, aryl, N-arylamino, aryloxy, arylsulfonyl,N-arylsulfonylamino, N-arylsulfonylamino C₁-C₆ alkylamino,N-arylsulfonylamino C₁-C₁₀ alkylcarbamoyl, arylsulfonylamino C₁-C₆alkoxycarbonyl, C₂-C₆ alkanoyl, N—C₂-C₆ alkanoylamino, aroyl,N-aroylamino, N-aroyl C₁-C₆ alkylamino, N-aroyl C₁-C₁₀ alkylcarbamoyl,N—C₁-C₆ alkylamino, N,N-di-C₁-C₆ alkylamino, N—C₁-C₁₀ alkylcarbamoyl,N,N-di-C₁-C₁₀ alkylcarbamoyl, N—C₁-C₆ alkylsulfamoyl, C₁-C₆alkylsulfinyl, C₁-C₆ alkylsulfonyl, C₁-C₆ alkylthio, C₁-C₆ alkoxy, C₁-C₆alkoxycarbonyl, N—C₃-C₆ cycloalkylamino, C₃-C₆ cycloalkyloxy and N—C₃-C₆cycloalkylcarbamoyl; or straight-chain or branched and saturated orunsaturated C₁-C₉ aliphatic groups, N—C₁-C₆ alkylamino groups, C₁-C₆alkylthio groups, or C₁-C₆ alkoxy groups, each of which groups may besubstituted with the above group,

[0202] R^(3c) and R^(4c) may be the same or different, and represent

[0203] (1) groups selected from the group consisting of hydrogen, azido,amidino, amino, carbamoyl, carbamoylamino, carbamoyloxy, carboxyl,guanidino, cyano, sulfamoyl, sulfo, nitro, halogen, hydroxy, formyl,formylamino, cyclic saturated C₃-C₉ aliphatic groups, cyclic unsaturatedC₃-C₉ aliphatic groups, C₂-C₆ alkanoyl, N—C₂-C₆ alkanoylamino, N—C₁-C₆alkylamino, N,N-di-C₁-C₆ alkylamino, N—C₁-C₁₀ alkylcarbamoyl,N,N-di-C₁-C₁₀ alkylcarbamoyl, C₁-C₆ alkylthio, N—C₁-C₆ alkylsulfamoyl,C₁-C₆ alkylsulfinyl, C₁-C₆ alkylsulfonyl, C₁-C₆ alkoxy, C₁-C₆alkoxycarbonyl, N—C₃-C₆ cycloalkylamino, C₃-C₆ cycloalkyloxy and N—C₃-C₆cycloalkylcarbamoyl,

[0204] (2) straight-chain or branched and saturated or unsaturated C₁-C₉aliphatic groups optionally be substituted with the above-mentionedgroup,

[0205] (3) (3-1) aryl groups; (3-2) monocyclic to tricyclic C₇-C₁₅aromatic carbocyclic groups (excluding aryl groups); (3-3) 5- or6-membered heterocyclic groups; (3-4) monocyclic to tricyclic aromaticheterocyclic groups having per one ring 1 to 5 hetero atoms selectedfrom the group consisting of nitrogen atoms, oxygen atoms and sulfuratoms (excluding 5- or 6-membered heterocyclic groups); or (3-5)straight-chain or branched and saturated or unsaturated C₁-C₉ aliphaticgroups optionally substituted with the above-mentioned aryl group,aromatic carbocyclic group, heterocyclic group or aromatic heterocyclicgroup;

[0206] each of which groups (3-1) to (3-5) may optionally be substitutedwith substituent(s), or

[0207] (4) R³c and R⁴c combine together to form a straight-chain orbranched unsaturated C₁-C₉ aliphatic group, or a 5- or 6-memberedsaturated or unsaturated carbocyclic group,

[0208] X_(1c) and X_(2c) are the same or different, and represent anoxygen atom or a sulfur atom,

[0209] Y_(c) represents an oxygen atom, a sulfur atom, a group CHR^(5c)or a group NR^(5c) (wherein R^(5c) represents a group selected from thegroup consisting of hydrogen, halogen, hydroxy, C₁-C₆ alkoxy, C₂-C₆alkanoyl, carbamoyl and N—C₁-C₁₀ alkylcarbamoyl; or a straight-chain orbranched and saturated or unsaturated C₁-C₉ aliphatic group optionallysubstituted with the above-mentioned group), and

[0210] Z_(c) represents a condensed aryl group; a bi- or tricyclicsaturated or unsaturated C₆-C₁₅ condensed carbocyclic group (excluding acondensed aryl group); a 6-membered heterocyclic group; or a bi- ortricyclic condensed aromatic heterocyclic group having per one ring 1 to5 hetero atoms selected from the group consisting of nitrogen atoms,oxygen atoms and sulfur atoms (excluding a 6-membered heterocyclicgroup)].

[0211] The compounds of the general formula [I] include compoundsrepresented by the general formula [I-1]

[0212] (wherein R, R¹, R², R³, R⁴, and Z are as defined before),compounds represented by the general formula [I-2]

[0213] (wherein R, R¹, R², R³, R⁴, R⁵, and Z are as defined before),compounds represented by the general formula [I-3]

[0214] (wherein X′₁ represents an oxygen atom or a group N(R⁵), X′₂represents an oxygen atom or a sulfur atom, and R, R¹, R², R³, R⁴, R⁵,R⁶, R⁷ and Z are as defined before). and compounds represented by thegeneral formula [I-4]

[0215] (wherein R, R¹, R², R³, R⁴ and Z are as defined before), andpreferred among them are compounds of the general formula [I-1],compounds of the general formula [I-3] and compounds of the generalformula [I-4], and particularly preferred among them are compounds ofthe general formula [I-1] and compounds of the general formula [I-3].

[0216] Representative examples of the compounds of the general formula[I] of the invention are shown in tables 1 to 45. TABLE 1 [I-1]

Com- pound No. R¹ R² R³ R⁴ Z R 1001 H H i-Pr H Ph 2-MeO—Ph 1002 H H i-PrH Ph Ph 1003 H H i-Pr H Ph 2-NH₂—Ph 1004 H H i-Pr H Ph 4-F—Ph 1005 H Hi-Pr H Ph 4-Et₂N—Ph 1006 H H i-Pr H Ph 4-Cl—Ph 1007 H H i-Pr H Ph4-HO—Ph 1008 H H i-Pr H Ph 3-MeO—Ph 1009 H H i-Pr H Ph 3-HO—Ph 1010 H Hi-Pr H Ph 3-NH₂—Ph 1011 H H i-Pr H Ph 4-MeO—Ph 1012 H H i-Pr H Ph4-Me—Ph 1013 H H i-Pr H Ph 3-Me—Ph 1014 H H i-Pr H Ph 4-tBuO₂CCH₂O—Ph1015 H H i-Pr H Ph 4-HO₂CCH₂O—Ph 1016 H H i-Pr H Ph 4-tBuO₂C(CH₂)₅O—Ph1017 H H i-Pr H Ph 4-HO₂C(CH₂)₅O—Ph 1018 H H i-Pr H Ph 4-HO(CH₂)₃O—Ph1019 H H i-Pr H Ph 4-HO(CH₂)₂O—Ph 1020 H H i-Pr H Ph4-HOC(Me)₂(CH₂)₂O—Ph 1021 H H i-Pr H Ph 4-PhCH₂O—Ph 1022 H H i-Pr H Ph4-MeNHCOCH₂O—Ph 1023 H H i-Pr H Ph 4-EtNHCOCH₂O—Ph 1024 H H i-Pr H Ph4-nPrNHCOCH₂O—Ph 1025 H H i-Pr H Ph 4-nBuNHCOCH₂O—Ph 1026 H H i-Pr H Ph4-CH₂═CHCH₂NHCOCH₂O—Ph 1027 H H i-Pr H Ph 4-Me(CH₂)₉NHCOCH₂O—Ph 1028 H Hi-Pr H Ph 4-N₃(CH₂)₃O—Ph 1029 H H i-Pr H Ph 4-tBuO₂CCH(Me)O—Ph 1030 H Hi-Pr H Ph 4-nPrNHCOCH(Me)O—Ph 1031 H H i-Pr H Ph 4-F₃CSO₃—Ph 1032 H Hi-Pr H Ph 4-tBuO₂CCH═CHPh 1033 H H i-Pr H Ph 4-nPrNHCOCH═CH—Ph 1034 H Hi-Pr H Ph 4-nPrCH(Me)NHCOCH₂O—Ph 1035 H H i-Pr H Ph4-EtCH(Me)NHCOCH₂O—Ph 1036 H H i-Pr H Ph 4-MeOCH₂O—Ph 1037 H H i-Pr H Ph4-EtCOCH₂O—Ph 1038 H H i-Pr H Ph 3-tBuO₂CCH₂O—Ph 1039 H H i-Pr H Ph3-HO₂CCH₂O—Ph 1040 H H i-Pr H Ph 3-nPrNHCOCH₂O—Ph 1041 H H i-Pr H Ph4-H2NC(Me)₂CH₂O₂CCH₂O—Ph 1042 H H i-Pr H Ph 4-morpholinoCOCH₂O—Ph 1043 HH i-Pr H Ph 4-(4-Cl—Ph)—COCH₂O—Ph 1044 H H i-Pr H Ph 4-PhCOCH₂O—Ph 1045H H i-Pr H Ph 4-(4-pyridyl)-CH₂NHCOCH₂O—Ph 1046 H H i-Pr H Ph4-H₂NCH₂CH₂NHCOCH₂O—Ph

[0217] TABLE 2 [I-1]

Compound No. R¹ R² R³ R⁴ Z R 1047 H H i-Pr H Ph 4-Cl-3-NO₂—Ph 1048 H Hi-Pr H Ph 4-Cl-3-F—Ph 1049 H H i-Pr H Ph 4-Cl-3-Me—Ph 1050 H H i-Pr H Ph3-NH₂-4-Cl—Ph 1051 H H i-Pr H Ph 3-Cl-4-MeO—Ph 1052 H H i-Pr H Ph3-Cl-4-Me—Ph 1053 H H i-Pr H Ph 4-Br-3-Cl—Ph 1054 H H i-Pr H Ph4-Br-2-Cl—Ph 1055 H H i-Pr H Ph 4-F-3-Me—Ph 1056 H H i-Pr H Ph3-F-4-Me—Ph 1057 H H i-Pr H Ph 3-Br-4-HO—Ph 1058 H H i-Pr H Ph3-Br-4-MeO—Ph 1059 H H i-Pr H Ph 3-Br-4-F—Ph 1060 H H i-Pr H Ph3-F-4-PhPh 1061 H H i-Pr H Ph 4-HO-3-I—Ph 1062 H H i-Pr H Ph 5-HO-2-I—Ph1063 H H i-Pr H Ph 3-I-4-MeO—Ph 1064 H H i-Pr H Ph 2-I-5-MeO—Ph 1065 H Hi-Pr H Ph 4-MeO-3-Me—Ph 1066 H H i-Pr H Ph 4-HO(CH₂)₃O-3-I—Ph 1067 H Hi-Pr H Ph 4-HO(CH₂)₂O-3-I—Ph 1068 H H i-Pr H Ph 4-HOC(Me)₂(CH₂)₂O-3-I—Ph1069 H H i-Pr H Ph 4-tBuO₂O(CH₂)₄O-3-I—Ph 1070 H H i-Pr H Ph3-I-4—PhCH₂O—Ph 1071 H H i-Pr H Ph 4-H₂NCOCH₂O-3-I—Ph 1072 H H i-Pr H Ph3-I-4-MeNHCOCH₂O—Ph 1073 H H i-Pr H Ph 4-EtNHCOCH₂O-3-I—Ph 1074 H H i-PrH Ph 3-I-4-nPrNHCOCH₂O—Ph 1075 H H i-Pr H Ph 3-I-4-iPrNHCOCH₂O—Ph 1076 HH i-Pr H Ph 4-nBuNHCOCH₂O-3-I—Ph 1077 H H i-Pr H Ph 4-tBuNHCOCH₂O-3-I—Ph1078 H H i-Pr H Ph 4-iBuNHCOCH₂O—Ph 1079 H H i-Pr H Ph4-tBuO₂CCH₂O-3-I—Ph 1080 H H i-Pr H Ph 3-I-4-PhCH₂NHCOCH₂O—Ph 1081 H Hi-Pr H Ph 3-I-4-(2-tetrahydrofuryl)CH₂NHCOCH₂O—Ph 1082 H H i-Pr H Ph4-cycloPrNHCOCH₂O-3-I—Ph 1083 H H i-Pr H Ph 4-cycloPentylNHCOCH₂O-3-I—Ph1084 H H i-Pr H Ph 4-cycloHexylNHCOCH₂O-3-I—Ph 1085 H H i-Pr H Ph4-cycloPrNHCOCH₂O-3-F—Ph 1086 H H i-Pr H Ph 4-Me(CH₂)₉NHCOCH₂O-3-I—Ph1087 H H i-Pr H Ph 4-HO₂CCH₂O-3-I—Ph 1088 H H i-Pr H Ph4-N₃(CH₂)₃O-3-I—Ph 1089 H H i-Pr H Ph 3-I-4-nPrNHCO(CH₂)₄O—Ph 1090 H Hi-Pr H Ph 4-Et₂NCOCH₂O-3-I—Ph 1091 H H i-Pr H Ph 3-I-4-nPrN(Me)COCH₂O—Ph1092 H H i-Pr H Ph 3-Cl-4-nPrNHCOCH₂O—Ph

[0218] TABLE 3 [I-1]

Compound No. R¹ R² R³ R⁴ Z R 1093 H H i-Pr H Ph 3-Br-4-nPrNHCOCH₂O—Ph1094 H H i-Pr H Ph 3-F-4-nPrNHCOCH₂O—Ph 1095 H H i-Pr H Ph3-Me-4-nPrNHCOCH₂O—Ph 1096 H H i-Pr H Ph 4-EtNHCOCH₂O-3-F—Ph 1097 H Hi-Pr H Ph 3-I-4-iPrNHCOC(Me)₂CH₂O—Ph 1098 H H i-Pr H Ph3-Br-4-CH₂═CHCH₂NHCOCH₂O—Ph 1099 H H i-Pr H Ph 4-iBuNHCOCH₂O-3-F—Ph 1100H H i-Pr H Ph 3-tBuO₂CCH═CH-4-nPrNHCOCH₂O—Ph 1101 H H i-Pr H Ph3-HO₂CCH═CH-4-nPrNHCOCH₂O—Ph 1102 H H i-Pr H Ph3-I-4-MeOCH₂CH₂NHCOCH₂O—Ph 1103 H H i-Pr H Ph 3-F-4-HO—Ph 1104 H H i-PrH Ph 3-F-4-MeO—Ph 1105 H H i-Pr H Ph 3,4-methylenedioxyPh 1106 H H i-PrH Ph 3,4-ethylenedioxyPh 1107 H H i-Pr H Ph 3,4-Cl₂—Ph 1108 H H i-Pr HPh 3,4-Me₂—Ph 1109 H H i-Pr H Ph 3,4-F₂—Ph 1110 H H i-Pr H Ph3,4-(MeO)₂—Ph 1111 H H i-Pr H Ph 3,5-(MeO)₂—Ph 1112 H H i-Pr H Ph3,5-Me₂—Ph 1113 H H i-Pr H Ph 3,5-I₂-4-HO—Ph 1114 H H i-Pr H Ph2,4-I₂-5-HO—Ph 1115 H H i-Pr H Ph 3,5-I₂-4-MeO—Ph 1116 H H i-Pr H Ph2,4-I₂-5-MeO—Ph 1117 H H i-Pr H Ph 2,4,6-Me₃—Ph 1118 H H i-Pr H Ph4-HO(CH₂)₃O-3,5-I₂Ph 1119 H H i-Pr H Ph 3,5-I₂-4-nPrNHCOCH₂O—Ph 1120 H Hi-Pr H Ph 2-thienyl 1121 H H i-Pr H Ph 2-furyl 1122 H H i-Pr H Ph3-pyridyl 1123 H H i-Pr H Ph 2-naphthyl 1124 H H i-Pr H Ph5-F-1-naphthyl 1125 H H i-Pr H Ph dibenzothiophene-2-yl 1126 6-F H i-PrH Ph Ph 1127 7-F H i-Pr H Ph Ph 1128 8-F H i-Pr H Ph Ph 1129 9-F H i-PrH Ph Ph 1130 6-MeO H i-Pr H Ph Ph 1131 9-MeO H i-Pr H Ph Ph 1132 6-OH Hi-Pr H Ph Ph 1133 9-OH H i-Pr H Ph Ph 1134 7-NO₂ H i-Pr H Ph Ph 11358-NO₂ H i-Pr H Ph Ph 1136 9-NO₂ H i-Pr H Ph Ph 1137 6-NHPh H i-Pr H PhPh 1138 7-Me₂N H i-Pr H Ph Ph

[0219] TABLE 4 [I-1]

Compound No. R¹ R² R³ R⁴ Z R 1139 7-Me H i-Pr H Ph Ph 1140 8-Me H i-Pr HPh Ph 1141 7-t-Bu H i-Pr H Ph Ph 1142 8-t-Bu H i-Pr H Ph Ph 1143 7-Br Hi-Pr H Ph Ph 1144 8-Br H i-Pr H Ph Ph 1145 7-Cl H i-Pr H Ph Ph 1146 8-ClH i-Pr H Ph Ph 1147 7-Cl 8-Cl i-Pr H Ph Ph 1148 6-Cl 9-Cl i-Pr H Ph Ph1149 6-OH 9-I i-Pr H Ph Ph 1150 H H i-Pr H 1,2-naphthyl Ph 1151 H H i-PrH 2,3-naphthyl Ph 1152 H H i-Pr H cyclohexenyl Ph 1153 H H D-Leucine HPh Ph 1154 H H L-Leucine H Ph Ph 1155 H H D-NorLeucine H Ph Ph 1156 H HL-NorLeucine H Ph Ph 1157 H H D-AlloLeucine H Ph Ph 1158 H HL-AlloLeucine H Ph Ph 1159 H H D-NorValine H Ph Ph 1160 H H L-NorValineH Ph Ph 1161 H H D-Alanine H Ph Ph 1162 H H L-Alanine H Ph Ph 1163 H HD-Arginine H Ph Ph 1164 H H L-Arginine H Ph Ph 1165 H H D-Asparagine HPh Ph 1166 H H L-Asparagine H Ph Ph 1167 H H D-Glutamic Acid H Ph Ph1168 H H L-Glutamic Acid H Ph Ph 1169 H H D-Glutamine H Ph Ph 1170 H HL-Glutamine H Ph Ph 1171 H H D-Histidine H Ph Ph 1172 H H L-Histidine HPh Ph 1173 H H D-Methionine H Ph Ph 1174 H H L-Methionine H Ph Ph 1175 HH D-Tryptophan H Ph Ph 1176 H H L-Tryptophan H Ph Ph 1177 H H D-TyrosineH Ph Ph 1178 H H L-Tyrosine H Ph Ph 1179 H H D-Homo Phenylalanine H PhPh 1180 H H L-Homo Phenylalanine H Ph Ph 1181 H H D-Leucine H Ph 4-Cl—Ph1182 H H L-Leucine H Ph 4-Cl—Ph 1183 H H D-NorLeucine H Ph 4-Cl—Ph

[0220] TABLE 5 [1-1]

Compound No. R¹ R² R³ R⁴ Z R 1184 H H L-NorLeucine H Ph 4-Cl—Ph 1185 H HD-AlloLeucine H Ph 4-Cl—Ph 1186 H H L-AlloLeucine H Ph 4-Cl—Ph 1187 H HD-NorValine H Ph 4-Cl—Ph 1188 H H L-NorValine H Ph 4-Cl—Ph 1189 H HD-Alanine H Ph 4-Cl—Ph 1190 H H L-Alanine H Ph 4-Cl—Ph 1191 H HD-Arginine H Ph 4-Cl—Ph 1192 H H L-Arginine H Ph 4-Cl—Ph 1193 H HD-Asparagine H Ph 4-Cl—Ph 1194 H H L-Asparagine H Ph 4-Cl—Ph 1195 H HD-Glutamic Acid H Ph 4-Cl—Ph 1196 H H L-Glutamic Acid H Ph 4-Cl—Ph 1197H H D-Glutamine H Ph 4-Cl—Ph 1198 H H L-Glutamine H Ph 4-Cl—Ph 1199 H HD-Histidine H Ph 4-Cl—Ph 1200 H H L-Histidine H Ph 4-Cl—Ph 1201 H HD-Methionine H Ph 4-Cl—Ph 1202 H H L-Methionine H Ph 4-Cl—Ph 1203 H HD-Tryptophan H Ph 4-Cl—Ph 1204 H H L-Tryptophan H Ph 4-Cl—Ph 1205 H HD-Tyrosine H Ph 4-Cl—Ph 1206 H H L-Tyrosine H Ph 4-Cl—Ph 1207 H H D-HomoPhenylalanine H Ph 4-Cl—Ph 1208 H H L-Homo Phenylalanine H Ph 4-Cl—Ph1209 H H t-Bu H Ph Ph 1210 H H (CH₃)₂(OH)C H Ph Ph 1211 H H CH₃(MeO)CH HPh Ph 1212 H H 4-HO—Ph H Ph Ph 1213 H H 4-HO-3-I—Ph H Ph Ph 1214 H H4-HO-3,5-I₂—Ph H Ph Ph 1215 H H 4-HO-3-I—PhCH₂ H Ph Ph 1216 H H4-HO-3,5-I₂—PhCH₂ H Ph Ph 1217 H H 1-naphthylmethyl H Ph Ph 1218 H H4-F—PhCH₂ H Ph Ph 1219 H H 1-naphthylmethyl H Ph 4-Cl—Ph 1220 H H4-F—PhCH₂ H Ph 4-Cl—Ph 1221 H H i-Pr Me Ph 4-Cl—Ph 1222 H H Me Me Ph Ph1223 H H (Combined with R⁴) CH₂═ — Ph Ph 1224 H H (Combined with R⁴)MeCH═ — Ph Ph 1225 H H (Combined with R⁴) (CH₂)₄ — Ph Ph 1226 H H i-Pr HPh 4-n-PrNHCOCH₂CH₂O—Ph 1227 H H i-Pr H Ph 4-i-PrNHCOCH₂CH₂O—Ph 1228 H Hi-Pr H Ph 4-EtNHCOCH₂CH₂O—Ph

[0221] TABLE 6 [I-1]

Com- pound No. R¹ R² R³ R⁴ Z R 1229 H H i-Pr H Ph4-EtCH(Me)NHCOCH₂CH₂O—Ph 1230 H H i-Pr H Ph 3-Cl-4-i-PrNHCOCH₂O—Ph 1231H H i-Pr H Ph 3-Cl-4-EtNHCOCH₂O—Ph 1232 H H i-Pr H Ph3-Cl-4-EtCH(Me)NHCOCH₂O—Ph 1233 H H i-Pr H Ph 4-i-PrNHCOCH₂O-3-Me—Ph1234 H H i-Pr H Ph 4-EtNHCOCH₂O-3-Me—Ph 1235 H H i-Pr H Ph4-EtCH(Me)NHCOCH₂O-3-Me—Ph 1236 H H i-Pr H Ph 4-cycloPrNHCOCH₂CH₂O—Ph1237 H H i-Pr H Ph 4-cycloPentylNHCOCH₂CH₂O—Ph 1238 H H i-Pr H Ph3-I-4-n-PrNHCOCH₂CH₂O—Ph 1239 H H i-Pr H Ph 3-I-4-i-PrNHCOCH₂CH₂O—Ph1240 H H i-Pr H Ph 4-EtNHCOCH₂CH₂O-3-I—Ph 1241 H H i-Pr H Ph4-EtCH(Me)NHCOCH₂CH₂O- 3-I—Ph 1242 H H i-Pr H Ph 4-EtCOCH₂CH₂O-3-I—Ph1243 H H i-Pr H Ph 4-cycloPrNHCOCH₂CH₂O-3-I—Ph 1244 H H i-Pr H Ph4-cycloPentylNHCOCH₂CH₂O- 3-I—Ph 1245 H H i-Pr H Ph3-F-4-n-PrNHCOCH₂CH₂O—Ph 1246 H H i-Pr H Ph 3-F-4-i-PrNHCOCH₂CH₂O—Ph1247 H H i-Pr H Ph 4-EtNHCOCH₂CH₂O-3-F—Ph 1248 H H i-Pr H Ph4-EtCH(Me)NHCOCH₂CH₂O- 3-F—Ph 1249 H H i-Pr H Ph 4-EtCOCH₂CH₂O-3-F—Ph1250 H H i-Pr H Ph 3-F-4-i-BuNHCOCH₂CH₂O—Ph 1251 H H i-Pr H Ph4-cycloPrNHCOCH₂CH₂O-3-F—Ph 1252 H H i-Pr H Ph 3-Br-4-n-PrNHCOCH₂CH₂O—Ph1253 H H i-Pr H Ph 3-Br-4-i-PrNHCOCH₂CH₂O—Ph 1254 H H i-Pr H Ph3-Br-4-EtNHCOCH₂CH₂O—Ph 1255 H H i-Pr H Ph 3-Br-4-i-BuNHCOOH₂CH₂O—Ph1256 H H i-Pr H Ph 3-Cl-4-n-PrNHCOCH₂CH₂O—Ph 1257 H H i-Pr H Ph3-Cl-4-i-PrNHCOCH₂CH₂O—Ph 1258 H H i-Pr H Ph 3-Cl-4-EtNHCOCH₂CH₂O—Ph1259 H H i-Pr H Ph 3-Cl-4- EtCH(Me)NHCOCH₂CH₂O—Ph 1260 H H i-Pr H Ph3-Cl-4-cycloPrNHCOCH₂CH₂O—Ph 1261 H H i-Pr H Ph 3-Cl-4-cycloPentylNHCOCH₂CH₂O—Ph 1262 H H i-Pr H Ph 3-Me-4-n-PrNHCOCH₂CH₂O—Ph1263 H H i-Pr H Ph 4-i-PrNHCOCH₂CH₂O-3-Me—Ph 1264 H H i-Pr H Ph4-EtNHCOCH₂CH₂O-3-Me—Ph 1265 H H i-Pr H Ph 3-Me-4-MeNHCOCH₂CH₂O—Ph 1266H H i-Pr H Ph 3-Me-4-n-BuNHCOCH₂CH₂O—Ph 1267 H H i-Pr H Ph4-EtCH(Me)NHCOCH₂CH₂O- 3-Me—Ph 1268 H H i-Pr H Ph 4-EtCOCH₂CH₂O-3-Me—Ph1269 H H i-Pr H Ph 4-i-BuNHCOCH₂CH₂O-3-Me—Ph 1270 H H i-Pr H Ph3-Me-4-t-BuNHCOCH₂CH₂O—Ph 1271 H H i-Pr H Ph 4-cycloPrNHCOCH₂CH₂O-3-Me—Ph 1272 H H i-Pr H Ph 4-cycloPentylNHCOCH₂CH₂O- 3-Me—Ph 1273 H H MeH Ph 3-Cl-4-n-PrNHCOCH₂O—Ph

[0222] TABLE 7 [I-1]

Com- pound No. R¹ R² R³ R⁴ Z R 1274 H H Me H Ph 3-Cl-4-i-PrNHCOCH₂O—Ph1275 H H Me H Ph 3-Cl-4-EtNHCOCH₂O—Ph 1276 H H Me H Ph 3-Cl-4-EtCH(Me)NHCOCH₂O—Ph 1277 H H Me H Ph 3-Cl-4-cycloPrNHCOCH₂O—Ph 1278 H HMe H Ph 3-Cl-4- cycloPentylNHCOCH₂O—Ph 1279 H H Et H Ph3-Me-4-n-PrNHCOCH₂O—Ph 1280 H H Et H Ph 4-i-PrNHCOCH₂O-3-Me—Ph 1281 H HEt H Ph 4-EtNHCOCH₂O-3-Me—Ph 1282 H H Et H Ph 3-Me-4-MeNHCOCH₂O—Ph 1283H H Et H Ph 3-Me-4-n-BuNHCOCH₂O—Ph 1284 H H Et H Ph 4-EtCH(Me)NHCOCH₂O-3-Me—Ph 1285 H H Et H Ph 4-EtCOCH₂O-3-Me—Ph 1286 H H Et H Ph4-i-BuNHCOCH₂O-3-Me—Ph 1287 H H Pr H Ph 3-Cl-4-n-PrNHCOCH₂O—Ph 1288 H HPr H Ph 3-Cl-4-i-PrNHCOCH₂O—Ph 1289 H H Pr H Ph 3-Cl-4-EtNHCOCH₂O—Ph1290 H H Pr H Ph 3-Cl-4- EtCH(Me)NHCOCH₂O—Ph 1291 H H Pr H Ph3-Cl-4-cycloPrNHCOCH₂O—Ph 1292 H H Pr H Ph 3-Cl-4-cycloPentylNHCOCH₂O—Ph 1293 H H Bu H Ph 3-Me-4-n-PrNHCOCH₂O—Ph 1294 H HBu H Ph 4-i-PrNHCOCH₂O-3-Me—Ph 1295 H H Bu H Ph 4-EtNHCOCH₂O-3-Me—Ph1296 H H Bu H Ph 3-Me-4-MeNHCOCH₂O—Ph 1297 H H Bu H Ph3-Me-4-n-BuNHCOCH₂O—Ph 1298 H H Bu H Ph 4-EtCH(Me)NHCOCH₂O- 3-Me—Ph 1299H H Bu H Ph 4-EtCOCH₂O-3-Me—Ph 1300 H H Bu H Ph 4-i-BuNHCOCH₂O-3-Me—Ph1301 H H i-Bu H Ph 3-Cl-4-n-PrNHCOCH₂O—Ph 1302 H H i-Bu H Ph3-Cl-4-i-PrNHCOCH₂O—Ph 1303 H H i-Bu H Ph 3-Cl-4-EtNHCOCH₂O—Ph 1304 H Hi-Bu H Ph 3-Cl-4- EtCH(Me)NHCOCH₂O—Ph 1305 H H i-Bu H Ph3-Cl-4-cycloPrNHCOCH₂O—Ph 1306 H H i-Bu H Ph 3-Cl-4-cycloPentylNHCOCH₂O—Ph 1307 H H t-Bu H Ph 3-Me-4-n-PrNHCOCH₂O—Ph 1308 HH t-Bu H Ph 4-i-PrNHCOCH₂O-3-Me—Ph 1309 H H t-Bu H Ph4-EtNHCOCH₂O-3-Me—Ph 1310 H H t-Bu H Ph 3-Me-4-MeNHCOCH₂O—Ph 1311 H HPhCH₂ H Ph 3-Me-4-n-BuNHCOCH₂O—Ph 1312 H H PhCH₂ H Ph4-EtCH(Me)NHCOCH₂O- 3-Me—Ph 1313 H H PhCH₂ H Ph 4-EtCOCH₂O-3-Me—Ph 1314H H PhCH₂ H Ph 4-i-BuNHCOCH₂O-3-Me—Ph 1315 H H i-Pr Me Ph3-Cl-4-n-PrNHCOCH₂O—Ph 1316 H H i-Pr Me Ph 3-Cl-4-i-PrNHCOCH₂O—Ph 1317 HH i-Pr Me Ph 3-Cl-4-EtNHCOCH₂O—Ph 1318 H H i-Pr Me Ph 3-Cl-4-EtCH(Me)NHCOCH₂O—Ph

[0223] TABLE 8 [I-9]

Compound No. R¹ R² R³ R⁴ Z R 1319 H H i-Pr Me Ph3-Cl-4-cycloPrNHCOCH₂O—Ph 1320 H H i-Pr Me Ph3-Cl-4-cycloPentylNHCOCH₂O—Ph 1321 H H i-Pr H 2,3-Pyridyl3-Me-4-n-PrNHCOCH₂O—Ph 1322 H H i-Pr H 2,3-Pyridyl4-i-PrNHCOCH₂O-3-Me—Ph 1323 H H i-Pr H 2,3-Pyridyl 4-EtNHCOCH₂O-3-Me—Ph1324 H H i-Pr H 2,3-Pyridyl 3-Me-4-MeNHCOCH₂O—Ph 1325 H H i-Pr H2,3-Pyridyl 3-Me-4-n-BuNHCOCH₂O—Ph 1326 H H i-Pr H 2,3-Pyridyl4-EtCH(Me)NHCOCH₂O-3-Me—Ph 1327 H H i-Pr H 2,3-Pyridyl4-EtCOCH₂O-3-Me—Ph 1328 H H i-Pr H 2,3-Pyridyl 4-i-BuNHCOCH₂O-3-Me—Ph1329 H H i-Pr H 2,3-Pyridyl 3-Cl-4-n-PrNHCOCH₂O—Ph 1330 H H i-Pr H3,4-Pyridyl 3-Cl-4-i-PrNHCOCH₂O—Ph 1331 H H i-Pr H 3,4-Pyridyl3-Cl-4-EtNHCOCH₂O—Ph 1332 H H i-Pr H 3,4-Pyridyl3-Cl-4-EtCH(Me)NHCOCH₂O—Ph 1333 H H i-Pr H 3,4-Pyridyl3-Cl-4-cycloPrNHCOCH₂O—Ph 1334 H H i-Pr H 3,4-Pyridyl3-Cl-4-cycloPentylNHCOCH₂O—Ph 1335 H H i-Pr H Ph4-F-5-n-PrNHCOCH₂O-(2-pyridyl) 1336 H H i-Pr H Ph4-F-5-i-PrNHCOCH₂₂O-(2-pyridyl) 1337 H H i-Pr H Ph4-EtNHCOCH₂O-3-F-(2-pyridyl) 1338 H H i-Pr H Ph4-EtCH(Me)NHCOCH₂O-3-F-(2-pyridyl) 1339 H H i-Pr H Ph4-EtCOCH₂O-3-F-(2-pyridyl) 1340 H H i-Pr H Ph3-F-4-i-BuNHCOCH₂O-(2-pyridyl) 1341 H H i-Pr H Ph4-cycloPrNHCOCH₂O-3-F-(2-pyridyl) 1342 H H i-Pr H Ph5-I-6-n-PrNHCOCH₂O-(3-pyridyl) 1343 H H i-Pr H Ph5-I-6-i-PrNHCOCH₂O-(3-pyridyl) 1344 H H i-Pr H Ph6-EtNHCOCH₂O-5-I-(3-pyridyl) 1345 H H i-Pr H Ph6-EtCH(Me)NHCOCH₂O-5-I-(3-pyridyl) 1346 H H i-Pr H Ph6-EtCOCH₂O-5-I-(3-pyridyl) 1347 H H i-Pr H Ph6-cycloPrNHCOCH₂O-5-I-(3-pyridyl) 1348 H H i-Pr H Ph3-NO₂-4-n-PrNHCOCH₂O—Ph 1349 H H i-Pr H Ph 3-NO₂-4-i-PrNHCOCH₂O—Ph 1350H H i-Pr H Ph 4-EtNHCOCH₂O-3-NO₂—Ph 1351 H H i-Pr H Ph4-EtCH(Me)NHCOCH₂O-3-NO₂—Ph 1352 H H i-Pr H Ph 4-EtCOCH₂O-3-NO₂—Ph 1353H H i-Pr H Ph 4-i-BuNHCOCH₂O-3-NO₂—Ph 1354 H H i-Pr H Ph4-cycloPrNHCOCH₂O-3-NO₂—Ph 1355 H H i-Pr H Ph 3-MeO-4-n-PrNHCOCH₂O—Ph1356 H H i-Pr H Ph 3-MeO-4-i-PrNHCOCH₂O—Ph 1357 H H i-Pr H Ph4-EtNHCOCH₂O-3-MeO—Ph 1358 H H i-Pr H Ph 4-EtCH(Me)NHCOCH₂O-3-MeO—Ph1359 H H i-Pr H Ph 4-EtCOCH₂O-3-MeO—Ph 1360 H H i-Pr H Ph3-MeO-4-i-BuNHCOCH₂O—Ph 1361 H H i-Pr H Ph 4-cycloPrNHCOCH₂O-3-MeO—Ph1362 H H i-Pr H Ph 3-HO-4-n-PrNHCOCH₂O—Ph 1363 H H i-Pr H Ph3-HO-4-i-PrNHCOCH₂O—Ph

[0224] TABLE 9 [I-1]

Com- pound No. R¹ R² R³ R⁴ Z R 1364 H H i-Pr H Ph 4-EtNHCOCH₂O-3-HO—Ph1365 H H i-Pr H Ph 4-EtCH(Me)NHCOCH₂O-3-HO—Ph 1366 H H i-Pr H Ph4-EtCOCH₂O-3-HO—Ph 1367 H H i-Pr H Ph 3-HO-4-i-BuNHCOCH₂O—Ph 1368 H Hi-Pr H Ph 4-cycloPrNHCOCH₂O-3-HO—Ph 1369 H H i-Pr H Ph3-H₂NCH₂CH₂NHCOCH₂O—Ph 1370 H H i-Pr H Ph 2-H₂NCH₂CH₂NHCOCH₂O—Ph 1371 HH i-Pr H Ph 4-MeNHCH₂CH₂NHCOCH₂O—Ph 1372 H H i-Pr H Ph3-MeNHCH₂CH₂NHCOCH₂O—Ph 1373 H H i-Pr H Ph 2-MeNHCH₂CH₂NHCOCH₂O—Ph 1374H H i-Pr H Ph 4-Me₂NCH₂CH₂NHCOCH₂O—Ph 1375 H H i-Pr H Ph3-Me₂NCH₂CH₂NHCOCH₂O—Ph 1376 H H i-Pr H Ph 2-Me₂NCH₂CH₂NHCOCH₂O—Ph 1377H H i-Pr H Ph 4-H₂NCH₂CH₂NHCOCH₂O- 3-Cl—Ph 1378 H H i-Pr H Ph3-H₂NCH₂CH₂NHCOCH₂O- 4-Cl—Ph 1379 H H i-Pr H Ph 2-H₂NCH₂CH₂NHCOCH₂O-4-Cl—Ph 1380 H H i-Pr H Ph 4-MeNHCH₂CH₂NHCOCH₂O- 3-Me—Ph 1381 H H i-Pr HPh 3-MeNHCH₂CH₂NHCOCH₂O- 4-Me—Ph 1382 H H i-Pr H Ph2-MeNHCH₂CH₂NHCOCH₂O- 4-Me—Ph 1383 H H i-Pr H Ph 4-Me₂NCH₂CH₂NHCOCH₂O-3-F—Ph 1384 H H i-Pr H Ph 3-Me₂NCH₂CH₂NHCOCH₂O- 4-F—Ph 1385 H H i-Pr HPh 2-Me₂NCH₂CH₂NHCOCH₂O- 4-F—Ph 1386 H H i-Pr H Ph 4-H₂NCOCH₂-3-I—Ph1387 H H i-Pr H Ph 3-I-4-MeNHCOCH₂—Ph 1388 H H i-Pr H Ph4-EtNHCOCH₂-3-I—Ph 1389 H H i-Pr H Ph 3-I-4-nPrNHCOCH₂—Ph 1390 H H i-PrH Ph 3-I-4-iPrNHCOCH₂—Ph 1391 H H i-Pr H Ph 4-nBuNHCOCH₂-3-I—Ph 1392 H Hi-Pr H Ph 4-tBuNHCOCH₂-3-I—Ph 1393 H H i-Pr H Ph 4-iBuNHCOCH₂—Ph 1394 HH i-Pr H Ph 4-tBuO₂CCH₂-3-I—Ph 1395 H H i-Pr H Ph 3-I-4—PhCH₂NHCOCH₂—Ph1396 H H i-Pr H Ph 3-I-4- (2-tetrahydrofuryl)CH₂NHCOCH₂— 1397 H H i-Pr HPh 4-cycloPrNHCOCH₂-3-I—Ph 1398 H H i-Pr H Ph4-cycloPentylNHCOCH₂-3-I—Ph 1399 H H i-Pr H Ph4-cycloHexylNHCOCH₂-3-I—Ph 1400 H H i-Pr H Ph 4-cycloPrNHCOCH₂-3-F—Ph1401 H H i-Pr H Ph 3-Cl-4-i-PrNHCOCH₂CH₂—Ph 1402 H H i-Pr H Ph3-Cl-4-EtNHCOCH₂CH₂—Ph 1403 H H i-Pr H Ph 3-Cl-4- EtCH(Me)NHCOCH₂CH₂—Ph1404 H H i-Pr H Ph 4-i-PrNHCO-3-Me—Ph 1405 H H i-Pr H Ph4-EtNHCO-3-Me—Ph 1406 H H i-Pr H Ph 4-EtCH(Me)NHCO-3-Me—Ph 1407 H H i-PrH Ph 3-Cl-4-i-PrNHCH₂CH₂O—Ph 1408 H H i-Pr H Ph 3-Cl-4-EtNHCH₂CH₂O—Ph1409 H H i-Pr H Ph 3-Cl-4-EtCH(Me)NHCH₂CH₂O—Ph

[0225] TABLE 10 [I-1]

Compound No. R¹ R² R³ R⁴ Z R 1410 H H i-Pr H 2,3-anthryl4-nBuNHCOCH₂O—Ph 1411 H H i-Pr H 2,3-indenyl 4-nPrNHCOCH₂O—Ph 1412 H Hi-Pr H 2,3-naphthyl 4-nPrNHCOCH₂O—Ph 1413 H H i-Pr H 2,3-pyrazinyl4-nPrNHCOCH₂O—Ph 1414 H H i-Pr H Ph 3-PhO-4-nPrNHCOCH₂O—Ph 1415 H H i-PrH Ph 3-PhCH₂O-4-MeO₂CNH₂CH₂NHCOCH₂O—Ph 1416 H H i-Pr H Ph3-Ph₂N-4-nPrNHCOCH₂O—Ph 1417 H H i-Pr H Ph 3-PhCH₂CH₂N-4-nPrNHCOCH₂O—Ph1418 H H i-Pr H Ph 3-PhCH₂CH₂N-4-nPrNHCOCH₂O—Ph 1419 H H i-Pr H Ph3-PhSO₃-4-nPrNHCOCH₂O—Ph 1420 H H i-Pr H Ph 3-Me-4-nPrNHCOCH₂S—Ph 1421 HH i-Pr H Ph 3-PhNHSO₂-4-nPrNHCOCH₂O—Ph 1422 H H i-Pr H Ph3-PhCH₂CO-4-nPrNHCOCH₂O—Ph 1423 H H H₂NCO—PhCH₂ H Ph 4-nPrNHCOCH₂O—Ph1424 H H MeCO—PhCH₂ H Ph 4-nPrNHCOCH₂O—Ph 1425 H H H₂NCH₂CH₂ H Ph4-nPrNHCOCH₂O—Ph 1426 H H MeO₂C—PhCH₂ H Ph 4-nPrNHCOCH₂O—Ph 1427 H HD-Glutamic Acid H Ph 3-Me-4-nPrNHCOCH₂O—Ph 1428 H H L-Glutamic Acid H Ph3-Me-4-nPrNHCOCH₂O—Ph 1429 H H (3-Pyridyl)CH₂ H Ph 3-Me-4-nPrNHCOCH₂O—Ph1430 H H i-Pr H Ph 4-n-PrNHCOCH₂O-3-CH₂CH—Ph 1431 H H i-Pr H Ph4-n-PrNHCOCH₂O-3-(2-Pyridyl)-Ph 1432 H H i-Pr H Ph4-n-PrNHCOCH₂O-3-(3-Pyridyl)-Ph 1433 H H i-Pr H Ph4-n-PrNHCOCH₂O-3-(4-Pyridyl)-Ph 1434 H H i-Pr H Ph3-Ph-4-n-PrNHCOCH₂O—Ph 1435 H H i-Pr H Ph 3-Et-4-n-PrNHCOCH₂O—Ph 1436 HH i-Pr H Ph 3-n-Bu-4-n-PrNHCOCH₂O—Ph 1437 H H i-Pr H Ph 3-MeO-6-Me—Ph1438 H H i-Pr H Ph 3-HO-6-Me—Ph 1439 H H i-Pr H Ph6-Me-3-n-PrNHCOCH₂O—Ph

[0226] TABLE 11 [I-2]

Com- pound No. R¹ R² R³ R⁴ R⁵ Z R 2001 H H i-Pr H H Ph 2-MeO—Ph 2002 H Hi-Pr H H Ph Ph 2003 H H i-Pr H H Ph 2-NH₂—Ph 2004 H H i-Pr H H Ph 4-F—Ph2005 H H i-Pr H H Ph 4-Et₂N—Ph 2006 H H i-Pr H H Ph 4-Cl—Ph 2007 H Hi-Pr H H Ph 4-HO—Ph 2008 H H i-Pr H H Ph 3-MeO—Ph 2009 H H i-Pr H H Ph3-HO—Ph 2010 H H i-Pr H H Ph 3-NH₂—Ph 2011 H H i-Pr H H Ph 4-MeO—Ph 2012H H i-Pr H H Ph 4-Me—Ph 2013 H H i-Pr H H Ph 3-Me—Ph 2014 H H i-Pr H HPh 4-tBuO₂CCH₂O—Ph 2015 H H i-Pr H H Ph 4-HO₂CCH₂O—Ph 2016 H H i-Pr H HPh 4-tBuO₂C(CH₂)₅O—Ph 2017 H H i-Pr H H Ph 4-HO₂C(CH₂)₅O—Ph 2018 H Hi-Pr H H Ph 4-HO(CH₂)₃O—Ph 2019 H H i-Pr H H Ph 4-HO(CH₂)₂O—Ph 2020 H Hi-Pr H H Ph 4-HOC(Me)₂(CH₂)₂O—Ph 2021 H H i-Pr H H Ph 4-PhCH₂O—Ph 2022 HH i-Pr H H Ph 4-MeNHCOCH₂O—Ph 2023 H H i-Pr H H Ph 4-EtNHCOCH₂O—Ph 2024H H i-Pr H H Ph 4-nPrNHCOCH₂O—Ph 2025 H H i-Pr H H Ph 4-nBuNHCOCH₂O—Ph2026 H H i-Pr H H Ph 4- CH₂═CHCH₂NHCOCH₂O—Ph 2027 H H i-Pr H H Ph4-Me(CH₂)₉NHCOCH₂O—Ph 2028 H H i-Pr H H Ph 4-N₃(CH₂)₃O—Ph 2029 H H i-PrH H Ph 4-tBuO₂CCH(Me)O—Ph 2030 H H i-Pr H H Ph 4-nPrNHCOCH(Me)O—Ph 2031H H i-Pr H H Ph 4-F₃CSO₃—Ph 2032 H H i-Pr H H Ph 4-tBuO₂CCH═CHPh 2033 HH i-Pr H H Ph 4-nPrNHCOCH═CH—Ph 2034 H H i-Pr H H Ph4-nPrCH(Me)NHCOCH₂O—Ph 2035 H H i-Pr H H Ph 4-EtCH(Me)NHCOCH₂O—Ph 2036 HH i-Pr H H Ph 4-MeOCH₂O—Ph 2037 H H i-Pr H H Ph 4-EtCOCH₂O—Ph 2038 H Hi-Pr H H Ph 3-tBuO₂CCH₂O—Ph 2039 H H i-Pr H H Ph 3-HO₂CCH₂O—Ph 2040 H Hi-Pr H H Ph 3-nPrNHCOCH₂O—Ph 2041 H H i-Pr H H Ph 4-H2NC(Me)₂CH₂O₂CCH₂O—Ph 2042 H H i-Pr H H Ph 4-morpholinoCOCH₂O—Ph 2043 HH i-Pr H H Ph 4-(4-Cl—Ph)—COCH₂O—Ph 2044 H H i-Pr H H Ph 4-PhCOCH₂O—Ph2045 H H i-Pr H H Ph 4-(4-pyridyl)- CH₂NHCOCH₂O—Ph 2046 H H i-Pr H H Ph4- H₂NCH₂CH₂NHCOCH₂O—Ph 2047 H H i-Pr H H Ph 4-Cl-3-NO₂—Ph

[0227] TABLE 12 [I-2]

Compound No. R¹ R² R³ R⁴ R⁵ Z R 2048 H H i-Pr H H Ph 4-Cl-3-F—Ph 2049 HH i-Pr H H Ph 4-Cl-3-Me—Ph 2050 H H i-Pr H H Ph 3-NH₂-4-Cl—Ph 2051 H Hi-Pr H H Ph 3-Cl-4-MeO—Ph 2052 H H i-Pr H H Ph 3-Cl-4-Me—Ph 2053 H Hi-Pr H H Ph 4-Br-3-Cl—Ph 2054 H H i-Pr H H Ph 4-Br-2-CF—Ph 2055 H H i-PrH H Ph 4-F-3-Me—Ph 2056 H H i-Pr H H Ph 3-F-4-Me—Ph 2057 H H i-Pr H H Ph3-Br-4-HO—Ph 2058 H H i-Pr H H Ph 3-Br-4-MeO—Ph 2059 H H i-Pr H H Ph3-Br-4-F—Ph 2060 H H i-Pr H H Ph 3-F-4-PhPh 2061 H H i-Pr H H Ph4-HO-3-I—Ph 2062 H H i-Pr H H Ph 5-HO-2-I—Ph 2063 H H i-Pr H H Ph3-I-4-MeO—Ph 2064 H H i-Pr H H Ph 2-I-5-MeO—Ph 2065 H H i-Pr H H Ph4-MeO-3-Me—Ph 2066 H H i-Pr H H Ph 4-HO(CH₂)₃O-3-I—Ph 2067 H H i-Pr H HPh 4-HO(CH₂)₂O-3-I—Ph 2068 H H i-Pr H H Ph 4-HOC(Me)₂(CH₂)₂O-3-I—Ph 2069H H i-Pr H H Ph 4-tBuO₂C(CH₂)₄O-3-I—Ph 2070 H H i-Pr H H Ph3-I-4-PhCH₂O—Ph 2071 H H i-Pr H H Ph 4-H₂NCOCH₂O-3-I—Ph 2072 H H i-Pr HH Ph 3-I-4-MeNHCOCH₂O—Ph 2073 H H i-Pr H H Ph 4-EtNHCOCH₂O-3-I—Ph 2074 HH i-Pr H H Ph 3-I-4-nPrNHCOCH₂O—Ph 2075 H H i-Pr H H Ph3-I-4-iPrNHCOCH₂O—Ph 2076 H H i-Pr H H Ph 4-nBuNHCOCH₂O-3-I—Ph 2077 H Hi-Pr H H Ph 4-tBuNHCOCH₂O-3-I—Ph 2078 H H i-Pr H H Ph 4-iBuNHCOCH₂O—Ph2079 H H i-Pr H H Ph 4-tBuO₂CCH₂O-3-I—Ph 2080 H H i-Pr H H Ph3-I-4-PhCH₂NHCOCH₂O—Ph 2081 H H i-Pr H H Ph3-I-4-(2-tetrahydrofuryl)CH₂NHCOCH₂O—Ph 2082 H H i-Pr H H Ph4-cycloPrNHCOCH₂O-3-I—Ph 2083 H H i-Pr H H Ph4-cycloPentylNHCOCH₂O-3-I—Ph 2084 H H i-Pr H H Ph4-cycloHexylNHCOCH₂O-3-I—Ph 2085 H H i-Pr H H Ph4-cycloPrNHCOCH₂O-3-I—Ph 2086 H H i-Pr H H Ph 4-Me(CH₂)₉NHCOCH₂O-3-I—Ph2087 H H i-Pr H H Ph 4-HO₂CCH₂O-3-I—Ph 2088 H H i-Pr H H Ph4-N₃(CH₂)₃O-3-I—Ph 2089 H H i-Pr H H Ph 3-I-4-nPrNHCO(CH₂)₄O—Ph 2090 H Hi-Pr H H Ph 4-Et₂NCOCH₂O-3-I—Ph 2091 H H i-Pr H H Ph3-I-4-nPrN(Me)COCH₂O—Ph 2092 H H i-Pr H H Ph 3-Cl-4-nPrNHCOCH₂O—Ph 2093H H i-Pr H H Ph 3-Br-4-nPrNHCOCH₂O—Ph 2094 H H i-Pr H H Ph3-F-4-nPrNHCOCH₂O—Ph

[0228] TABLE 13 [I-2]

Compound No. R¹ R² R³ R⁴ R⁵ Z R 2095 H H i-Pr H H Ph3-Me-4-nPrNHCOCH₂O—Ph 2096 H H i-Pr H H Ph 4-EtNHCOCH₂O-3-F—Ph 2097 H Hi-Pr H H Ph 3-I-4-iPrNHCOC(Me)₂CH₂O—Ph 2098 H H i-Pr H H Ph3-Br-4-CH₂═CHCH₂NHCOCH₂O—Ph 2099 H H i-Pr H H Ph 4-iBuNHCOCH₂O-3-F—Ph2100 H H i-Pr H H Ph 3-tBuO₂CCH═CH-4-nPrNHCOCH₂O—Ph 2101 H H i-Pr H H Ph3-HO₂CCH═CH-4-nPrNHCOCH₂O—Ph 2102 H H i-Pr H H Ph3-I-4-MeOCH₂CH₂NHCOCH₂O—Ph 2103 H H i-Pr H H Ph 3-F-4-HO—Ph 2104 H Hi-Pr H H Ph 3-F-4-MeO—Ph 2105 H H i-Pr H H Ph 3,4-methylenedioxyPh 2106H H i-Pr H H Ph 3,4-ethylenedioxyPh 2107 H H i-Pr H H Ph 3,4-Cl₂—Ph 2108H H i-Pr H H Ph 3,4-Me₂—Ph 2109 H H i-Pr H H Ph 3,4-F₂—Ph 2110 H H i-PrH H Ph 3,4-(MeO)₂—Ph 2111 H H i-Pr H H Ph 3,5-(MeO)₂—Ph 2112 H H i-Pr HH Ph 3,5-Me₂—Ph 2113 H H i-Pr H H Ph 3,5-I₂-4-HO—Ph 2114 H H i-Pr H H Ph2,4-I₂-5-HO—Ph 2115 H H i-Pr H H Ph 3,5-I₂-4-MeO—Ph 2116 H H i-Pr H H Ph2,4-I₂-5-MeO—Ph 2117 H H i-Pr H H Ph 2,4,6-Me₃—Ph 2118 H H i-Pr H H Ph4-HO(CH₂)₃O-3,5-I₂Ph 2119 H H i-Pr H H Ph 3,5-I₂-4-nPrNHCOCH₂O—Ph 2120 HH i-Pr H H Ph 2-thienyl 2121 H H i-Pr H H Ph 2-furyl 2122 H H i-Pr H HPh 3-pyridyl 2123 H H i-Pr H H Ph 2-naphthyl 2124 H H i-Pr H H Ph5-F-1-naphthyl 2125 H H i-Pr H H Ph dibenzothiophene-2-yl 2126 6-F Hi-Pr H H Ph Ph 2127 7-F H i-Pr H H Ph Ph 2128 8-F H i-Pr H H Ph Ph 21299-F H i-Pr H H Ph Ph 2130 6-MeO H i-Pr H H Ph Ph 2131 9-MeO H i-Pr H HPh Ph 2132 6-OH H i-Pr H H Ph Ph 2133 9-OH H i-Pr H H Ph Ph 2134 7-NO₂ Hi-Pr H H Ph Ph 2135 8-NO₂ H i-Pr H H Ph Ph 2136 9-NO₂ H i-Pr H H Ph Ph2137 6-NHPh H i-Pr H H Ph Ph 2138 7-Me₂N H i-Pr H H Ph Ph 2139 7-Me Hi-Pr H H Ph Ph 2140 8-Me H i-Pr H H Ph Ph 2141 7-t-Bu H i-Pr H H Ph Ph

[0229] TABLE 14 [I-2]

Compound No. R¹ R² R³ R⁴ R⁵ Z R 2142 8-t-Bu H i-Pr H H Ph Ph 2143 7-Br Hi-Pr H H Ph Ph 2144 8-Br H i-Pr H H Ph Ph 2145 7-Cl H i-Pr H H Ph Ph2146 8-Cl H i-Pr H H Ph Ph 2147 7-Cl 8-Cl i-Pr H H Ph Ph 2148 6-Cl 9-Cli-Pr H H Ph Ph 2149 6-OH 9-I i-Pr H H Ph Ph 2150 H H i-Pr H H1,2-naphthyl Ph 2151 H H i-Pr H H 2,3-naphthyl Ph 2152 H H i-Pr H Hcyclohexenyl Ph 2153 H H D-Leucine H H Ph Ph 2154 H H L-Leucine H H PhPh 2155 H H D-NorLeucine H H Ph Ph 2156 H H L-NorLeucine H H Ph Ph 2157H H D-AlloLeucine H H Ph Ph 2158 H H L-AlloLeucine H H Ph Ph 2159 H HD-NorValine H H Ph Ph 2160 H H L-NorValine H H Ph Ph 2161 H H D-AlanineH H Ph Ph 2162 H H L-Alanine H H Ph Ph 2163 H H D-Arginine H H Ph Ph2164 H H L-Arginine H H Ph Ph 2165 H H D-Asparagine H H Ph Ph 2166 H HL-Asparagine H H Ph Ph 2167 H H D-Glutamic Acid H H Ph Ph 2168 H HL-Glutamic Acid H H Ph Ph 2169 H H D-Glutamine H H Ph Ph 2170 H HL-Glutamine H H Ph Ph 2171 H H D-Histidine H H Ph Ph 2172 H HL-Histidine H H Ph Ph 2173 H H D-Methionine H H Ph Ph 2174 H HL-Methionine H H Ph Ph 2175 H H D-Tryptophan H H Ph Ph 2176 H HL-Tryptophan H H Ph Ph 2177 H H D-Tyrosine H H Ph Ph 2178 H H L-TyrosineH H Ph Ph 2179 H H D-Homo Phenylalanine H H Ph Ph 2180 H H L-HomoPhenylalanine H H Ph Ph 2181 H H D-Leucine H H Ph 4-Cl—Ph 2182 H HL-Leucine H H Ph 4-Cl—Ph 2183 H H D-NorLeucine H H Ph 4-Cl—Ph 2184 H HL-NorLeucine H H Ph 4-Cl—Ph 2185 H H D-AlloLeucine H H Ph 4-Cl—Ph 2186 HH L-AlloLeucine H H Ph 4-Cl—Ph 2187 H H D-NorValine H H Ph 4-Cl—Ph

[0230] TABLE 15 [I-2]

Compound No. R¹ R² R³ R⁴ R⁵ Z R 2188 H H L-NorValine H H Ph 4-Cl—Ph 2189H H D-Alanine H H Ph 4-Cl—Ph 2190 H H L-Alanine H H Ph 4-Cl—Ph 2191 H HD-Arginine H H Ph 4-Cl—Ph 2192 H H L-Arginine H H Ph 4-Cl—Ph 2193 H HD-Asparagine H H Ph 4-Cl—Ph 2194 H H L-Asparagine H H Ph 4-Cl—Ph 2195 HH D-Glutamic Acid H H Ph 4-Cl—Ph 2196 H H L-Glutamic Acid H H Ph 4-Cl—Ph2197 H H D-Glutamine H H Ph 4-Cl—Ph 2198 H H L-Glutamine H H Ph 4-Cl—Ph2199 H H D-Histidine H H Ph 4-Cl—Ph 2200 H H L-Histidine H H Ph 4-Cl—Ph2201 H H D-Methionine H H Ph 4-Cl—Ph 2202 H H L-Methionine H H Ph4-Cl—Ph 2203 H H D-Tryptophan H H Ph 4-Cl—Ph 2204 H H L-Tryptophan H HPh 4-Cl—Ph 2205 H H D-Tyrosine H H Ph 4-Cl—Ph 2206 H H L-Tyrosine H H Ph4-Cl—Ph 2207 H H D-Homo Phenylalanine H H Ph 4-Cl—Ph 2208 H H L-HomoPhenylalanine H H Ph 4-Cl—Ph 2209 H H t-Bu H H Ph Ph 2210 H H(CH₃)₂(OH)C H H Ph Ph 2211 H H CH₃(MeO)CH H H Ph Ph 2212 H H 4-HO—Ph H HPh Ph 2213 H H 4-HO-3-I—Ph H H Ph Ph 2214 H H 4-HO-3,5-I₂—Ph H H Ph Ph2215 H H 4-HO-3-I—PhCH₂ H H Ph Ph 2216 H H 4-HO-3,5-I₂—PhCH₂ H H Ph Ph2217 H H 1-naphthylmethyl H H Ph Ph 2218 H H 4-F—PhCH₂ H H Ph Ph 2219 HH 1-naphthylmethyl H H Ph 4-Cl—Ph 2220 H H 4-F—PhCH₂ H H Ph 4-Cl—Ph 2221H H i-Pr Me H Ph 4-Cl—Ph 2222 H H Me Me H Ph Ph 2223 H H (Combined withR⁴) CH₂═ — H Ph Ph 2224 H H (Combined with R⁴) MeCH═ — H Ph Ph 2225 H H(Combined with R⁴) (CH₂)₄ — H Ph Ph 2226 H H i-Pr H H Ph4-n-PrNHCOCH₂CH₂O—Ph 2227 H H i-Pr H H Ph 4-i-PrNHCOCH₂CH₂O—Ph 2228 H Hi-Pr H H Ph 4-EtNHCOCH₂CH₂O—Ph 2229 H H i-Pr H H Ph4-EtCH(Me)NHCOCH₂CH₂O—Ph 2230 H H i-Pr H H Ph 3-Cl-4-i-PrNHCOCH₂O—Ph2231 H H i-Pr H H Ph 3-Cl-4-EtNHCOCH₂O—Ph 2232 H H i-Pr H H Ph3-Cl-4-EtCH(Me)NHCOCH₂O—Ph 2233 H H i-Pr H H Ph 4-i-PrNHCOCH₂O-3-Me—Ph

[0231] TABLE 16 [I-2]

Compound No. R¹ R² R³ R⁴ R⁵ Z R 2234 H H i-Pr H H Ph4-EtNHCOCH₂O-3-Me—Ph 2235 H H i-Pr H H Ph 4-EtCH(Me)NHCOCH₂O-3-Me—Ph2236 H H i-Pr H H Ph 4-cycloPrNHCOCH₂CH₂O—Ph 2237 H H i-Pr H H Ph4-cycloPentylNHCOCH₂CH₂O—Ph 2238 H H i-Pr H H Ph3-I-4-n-PrNHCOCH₂CH₂O—Ph 2239 H H i-Pr H H Ph 3-I-4-i-PrNHCOCH₂CH₂O—Ph2240 H H i-Pr H H Ph 4-EtNHCOCH₂CH₂O-3-I—Ph 2241 H H i-Pr H H Ph4-EtCH(Me)NHCOCH₂CH₂O-3-I—Ph 2242 H H i-Pr H H Ph 4-EtCOCH₂CH₂O-3-I—Ph2243 H H i-Pr H H Ph 4-cycloPrNHCOCH₂CH₂O-3-I—Ph 2244 H H i-Pr H H Ph4-cycloPentylNHCOCH₂CH₂O-3-I—Ph 2245 H H i-Pr H H Ph3-F-4-n-PrNHCOCH₂CH₂O—Ph 2246 H H i-Pr H H Ph 3-F-4-i-PrNHCOCH₂CH₂O—Ph2247 H H i-Pr H H Ph 4-EtNHCOCH₂CH₂O-3-F—Ph 2248 H H i-Pr H H Ph4-EtCH(Me)NHCOCH₂CH₂O-3-F—Ph 2249 H H i-Pr H H Ph 4-EtCOCH₂CH₂O-3-F—Ph2250 H H i-Pr H H Ph 3-F-4-i-BuNHCOCH₂CH₂O—Ph 2251 H H i-Pr H H Ph4-cycloPrNHCOCH₂CH₂O-3-F—Ph 2252 H H i-Pr H H Ph3-Br-4-n-PrNHCOCH₂CH₂O—Ph 2253 H H i-Pr H H Ph 3-Br-4-i-PrNHCOCH₂CH₂O—Ph2254 H H i-Pr H H Ph 3-Br-4-EtNHCOCH₂CH₂O—Ph 2255 H H i-Pr H H Ph3-Br-4-i-BuNHCOCH₂CH₂O—Ph 2256 H H i-Pr H H Ph 3-Cl-4-n-PrNHCOCH₂CH₂O—Ph2257 H H i-Pr H H Ph 3-Cl-4-i-PrNHCOCH₂CH₂O—Ph 2258 H H i-Pr H H Ph3-Cl-4-EtNHCOCH₂CH₂O—Ph 2259 H H i-Pr H H Ph3-Cl-4-EtCH(Me)NHCOCH₂CH₂O—Ph 2260 H H i-Pr H H Ph3-Cl-4-cycloPrNHCOCH₂CH₂O—Ph 2261 H H i-Pr H H Ph3-Cl-4-cycloPentylNHCOCH₂CH₂O—Ph 2262 H H i-Pr H H Ph3-Me-4-n-PrNHCOCH₂CH₂O—Ph 2263 H H i-Pr H H Ph 4-i-PrNHCOCH₂CH₂O-3-Me—Ph2264 H H i-Pr H H Ph 4-EtNHCOCH₂CH₂O-3-Me—Ph 2265 H H i-Pr H H Ph3-Me-4-MeNHCOCH₂CH₂O—Ph 2266 H H i-Pr H H Ph 3-Me-4-n-BuNHCOCH₂CH₂O—Ph2267 H H i-Pr H H Ph 4-EtCH(Me)NHCOCH₂CH₂O-3-Me—Ph 2268 H H i-Pr H H Ph4-EtCOCH₂CH₂O-3-Me—Ph 2269 H H i-Pr H H Ph 4-i-BuNHCOCH₂CH₂O-3-Me—Ph2270 H H i-Pr H H Ph 3-Me-4-t-BuNHCOCH₂CH₂O—Ph 2271 H H i-Pr H H Ph4-cycloPrNHCOCH₂CH₂O-3-Me—Ph 2272 H H i-Pr H H Ph4-cycloPentylNHCOCH₂CH₂O-3-Me—Ph 2273 H H Me H H Ph3-Cl-4-n-PrNHCOCH₂O—Ph 2274 H H Me H H Ph 3-Cl-4-i-PrNHCOCH₂O—Ph 2275 HH Me H H Ph 3-Cl-4-EtNHCOCH₂O—Ph 2276 H H Me H H Ph3-Cl-4-EtCH(Me)NHCOCH₂O—Ph 2277 H H Me H H Ph 3-Cl-4-cycloPrNHCOCH₂O—Ph2278 H H Me H H Ph 3-Cl-4-cycloPentylNHCOCH₂O—Ph 2279 H H Et H H Ph3-Me-4-n-PrNHCOCH₂O—Ph

[0232] TABLE 17 [I-2]

Compound No. R¹ R² R³ R⁴ R⁵ Z R 2280 H H Et H H Ph4-i-PrNHCOCH₂O-3-Me—Ph 2281 H H Et H H Ph 4-EtNHCOCH₂O-3-Me—Ph 2282 H HEt H H Ph 3-Me-4-MeNHCOCH₂O—Ph 2283 H H Et H H Ph 3-Me-4-n-BuNHCOCH₂O—Ph2284 H H Et H H Ph 4-EtCH(Me)NHCOCH₂O-3-Me—Ph 2285 H H Et H H Ph4-EtCOCH₂O-3-Me—Ph 2286 H H Et H H Ph 4-i-BuNHCOCH₂O-3-Me—Ph 2287 H H PrH H Ph 3-Cl-4-n-PrNHCOCH₂O—Ph 2288 H H Pr H H Ph 3-Cl-4-i-PrNHCOOH₂O—Ph2289 H H Pr H H Ph 3-Cl-4-EtNHCOCH₂O—Ph 2290 H H Pr H H Ph3-Cl-4-EtCH(Me)NHCOCH₂O—Ph 2291 H H Pr H H Ph 3-Cl-4-cycloPrNHCOCH₂O—Ph2292 H H Pr H H Ph 3-Cl-4-cycloPentylNHCOCH₂O—Ph 2293 H H Bu H H Ph3-Me-4-n-PrNHCOCH₂O—Ph 2294 H H Bu H H Ph 4-i-PrNHCOCH₂O-3-Me—Ph 2295 HH Bu H H Ph 4-EtNHCOCH₂O-3-Me—Ph 2296 H H Bu H H Ph 3-Me-4-MeNHCOCH₂O—Ph2297 H H Bu H H Ph 3-Me-4-n-BuNHCOCH₂O—Ph 2298 H H Bu H H Ph4-EtCH(Me)NHCOCH₂O-3-Me—Ph 2299 H H Bu H H Ph 4-EtCOCH₂O-3-Me—Ph 2300 HH Bu H H Ph 4-i-BuNHCOCH₂O-3-Me—Ph 2301 H H i-Bu H H Ph3-Cl-4-n-PrNHCOCH₂O—Ph 2302 H H i-Bu H H Ph 3-Cl-4-i-PrNHCOCH₂O—Ph 2303H H i-Bu H H Ph 3-Cl-4-EtNHCOCH₂O—Ph 2304 H H i-Bu H H Ph3-Cl-4-EtCH(Me)NHCOCH₂O—Ph 2305 H H i-Bu H H Ph3-Cl-4-cycloPrNHCOCH₂O—Ph 2306 H H i-Bu H H Ph3-Cl-4-cycloPentylNHCOCH₂O—Ph 2307 H H t-Bu H H Ph3-Me-4-n-PrNHCOCH₂O—Ph 2308 H H t-Bu H H Ph 4-i-PrNHCOCH₂O-3-Me—Ph 2309H H t-Bu H H Ph 4-EtNHCOCH₂O-3-Me—Ph 2310 H H t-Bu H H Ph3-Me-4-MeNHCOCH₂O—Ph 2311 H H PhCH₂ H H Ph 3-Me-4-n-BuNHCOCH₂O—Ph 2312 HH PhCH₂ H H Ph 4-EtCH(Me)NHCOCH₂O-3-Me—Ph 2313 H H PhCH₂ H H Ph4-EtCOCH₂O-3-Me—Ph 2314 H H PhCH₂ H H Ph 4-i-BuNHCOCH₂O-3-Me—Ph 2315 H Hi-Pr Me H Ph 3-Cl-4-n-PrNHCOCH₂O—Ph 2316 H H i-Pr Me H Ph3-Cl-4-i-PrNHCOCH₂O—Ph 2317 H H i-Pr Me H Ph 3-Cl-4-EtNHCOCH₂O—Ph 2318 HH i-Pr Me H Ph 3-Cl-4-EtCH(Me)NHCOCH₂O—Ph 2319 H H i-Pr Me H Ph3-Cl-4-cycloPrNHCOCH₂O—Ph 2320 H H i-Pr Me H Ph3-Cl-4-cycloPentylNHCOCH₂O—Ph 2321 H H i-Pr H H 2,3-Pyridyl3-Me-4-n-PrNHCOCH₂O—Ph 2322 H H i-Pr H H 2,3-Pyridyl4-i-PrNHCOCH₂O-3-Me—Ph 2323 H H i-Pr H H 2,3-Pyridyl4-EtNHCOCH₂O-3-Me—Ph 2324 H H i-Pr H H 2,3-Pyridyl 3-Me-4-MeNHCOCH₂O—Ph2325 H H i-Pr H H 2,3-Pyridyl 3-Me-4-n-BuNHCOCH₂O—Ph

[0233] TABLE 18 [I-2]

Compound No. R¹ R² R³ R⁴ R⁵ Z R 2326 H H i-Pr H H 2,3-Pyridyl4-EtCH(Me)NHCOCH₂O-3-Me—Ph 2327 H H i-Pr H H 2,3-Pyridyl4-EtCOCH₂O-3-Me—Ph 2328 H H i-Pr H H 2,3-Pyridyl 4-i-BuNHCOCH₂O-3-Me—Ph2329 H H i-Pr H H 2,3-Pyridyl 3-Cl-4-n-PrNHCOCH₂O—Ph 2330 H H i-Pr H H3,4-Pyridyl 3-Cl-4-i-PrNHCOCH₂O—Ph 2331 H H i-Pr H H 3,4-Pyridyl3-Cl-4-EtNHCOCH₂O—Ph 2332 H H i-Pr H H 3,4-Pyridyl3-Cl-4-EtCH(Me)NHCOCH₂O—Ph 2333 H H i-Pr H H 3,4-Pyridyl3-Cl-4-cycloPrNHCOCH₂O—Ph 2334 H H i-Pr H H 3,4-Pyridyl3-Cl-4-cycloPentylNHCOCH₂O—Ph 2335 H H i-Pr H H Ph4-F-5-n-PrNHCOCH₂O-(2-pyridyl) 2336 H H i-Pr H H Ph4-F-5-i-PrNHCOCH₂₂O-(2-pyridyl) 2337 H H i-Pr H H Ph4-EtNHCOCH₂O-3-F-(2-pyridyl) 2338 H H i-Pr H H Ph4-EtCH(Me)NHCOCH₂O-3-F-(2-pyridyl) 2339 H H i-Pr H H Ph4-EtCOCH₂O-3-F-(2-pyridyl) 2340 H H i-Pr H H Ph3-F-4-i-BuNHCOCH₂O-(2-pyridyl) 2341 H H i-Pr H H Ph4-cycloPrNHCOCH₂O-3-F-(2-pyridyl) 2342 H H i-Pr H H Ph5-I-6-n-PrNHCOCH₂O-(3-pyridyl) 2343 H H i-Pr H H Ph5-I-6-i-PrNHCOCH₂O-(3-pyridyl) 2344 H H i-Pr H H Ph6-EtNHCOCH₂O-5-I-(3-pyridyl) 2345 H H i-Pr H H Ph6-EtCH(Me)NHCOCH₂O-5-I-(3-pyridyl) 2346 H H i-Pr H H Ph6-EtCOCH₂O-5-I-(3-pyridyl) 2347 H H i-Pr H H Ph6-cycloPrNHCOCH₂O-5-I-(3-pyridy 2348 H H i-Pr H H Ph3-NO₂-4-n-PrNHCOCH₂O—Ph 2349 H H i-Pr H H Ph 3-NO₂-4-i-PrNHCOCH₂O—Ph2350 H H i-Pr H H Ph 4-EtNHCOCH₂O-3-NO₂—Ph 2351 H H i-Pr H H Ph4-EtCH(Me)NHCOCH₂O-3-NO₂—Ph 2352 H H i-Pr H H Ph 4-EtCOCH₂O-3-NO₂—Ph2353 H H i-Pr H H Ph 4-i-BuNHCOCH₂O-3-NO₂—Ph 2354 H H i-Pr H H Ph4-cycloPrNHCOCH₂O-3-NO₂—Ph 2355 H H i-Pr H H Ph 3-MeO-4-n-PrNHCOCH₂O—Ph2356 H H i-Pr H H Ph 3-MeO-4-i-PrNHCOCH₂O—Ph 2357 H H i-Pr H H Ph4-EtNHCOCH₂O-3-MeO—Ph 2358 H H i-Pr H H Ph 4-EtCH(Me)NHCOCH₂O-3-MeO—Ph2359 H H i-Pr H H Ph 4-EtCOCH₂O-3-MeO—Ph 2360 H H i-Pr H H Ph3-MeO-4-i-BuNHCOCH₂O—Ph 2361 H H i-Pr H H Ph 4-cycloPrNHCOCH₂O-3-MeO—Ph2362 H H i-Pr H H Ph 3-HO-4-n-PrNHCOCH₂O—Ph 2363 H H i-Pr H H Ph3-HO-4-i-PrNHCOCH₂O—Ph 2364 H H i-Pr H H Ph 4-EtNHCOCH₂O-3-HO—Ph 2365 HH i-Pr H H Ph 4-EtCH(Me)NHCOCH₂O-3-HO—Ph 2366 H H i-Pr H H Ph4-EtCOCH₂O-3-HO—Ph 2367 H H i-Pr H H Ph 3-HO-4-i-BuNHCOCH₂O—Ph 2368 H Hi-Pr H H Ph 4-cycloPrNHCOCH₂O-3-HO—Ph 2369 H H i-Pr H H Ph3-H₂NCH₂CH₂NHCOCH₂O—Ph 2370 H H i-Pr H H Ph 2-H₂NCH₂CH₂NHCOCH₂O—Ph 2371H H i-Pr H H Ph 4-MeNHCH₂CH₂NHCOCH₂O—Ph

[0234] TABLE 19 [I-2]

Compound No. R¹ R² R³ R⁴ R⁵ Z R 2372 H H i-Pr H H Ph3-MeNHCH₂CH₂NHCOCH₂O—Ph 2373 H H i-Pr H H Ph 2-MeNHCH₂CH₂NHCOCH₂O—Ph2374 H H i-Pr H H Ph 4-Me₂NCH₂CH₂NHCOCH₂O—Ph 2375 H H i-Pr H H Ph3-Me₂NCH₂CH₂NHCOCH₂O—Ph 2376 H H i-Pr H H Ph 2-Me₂NCH₂CH₂NHCOCH₂O—Ph2377 H H i-Pr H H Ph 4-H₂NCH₂CH₂NHCOCH₂O-3-Cl—Ph 2378 H H i-Pr H H Ph3-H₂NCH₂CH₂NHCOCH₂O-4-Cl—Ph 2379 H H i-Pr H H Ph2-H₂NCH₂CH₂NHCOCH₂O-4-Cl—Ph 2380 H H i-Pr H H Ph4-MeNHCH₂CH₂NHCOCH₂O-3-Me—Ph 2381 H H i-Pr H H Ph3-MeNHCH₂CH₂NHCOCH₂O-4-Me—Ph 2382 H H i-Pr H H Ph2-MeNHCH₂CH₂NHCOCH₂O-4-MePh 2383 H H i-Pr H H Ph4-Me₂NCH₂CH₂NHCOCH₂O-3-F—Ph 2384 H H i-Pr H H Ph3-Me₂NCH₂CH₂NHCOCH₂O-4-F—Ph 2385 H H i-Pr H H Ph2-Me₂NCH₂CH₂NHCOCH₂O-4-F—Ph 2386 H H i-Pr H H Ph 4-H₂NCOCH₂-3-I—Ph 2387H H i-Pr H H Ph 3-I-4-MeNHCOCH₂—Ph 2388 H H i-Pr H H Ph4-EtNHCOCH₂-3-I—Ph 2389 H H i-Pr H H Ph 3-I-4-nPrNHCOCH₂—Ph 2390 H Hi-Pr H H Ph 3-I-4-iPrNHCOCH₂—Ph 2391 H H i-Pr H H Ph 4-nBuNHCOCH₂-3-I—Ph2392 H H i-Pr H H Ph 4-tBuNHCOCH₂-3-I—Ph 2393 H H i-Pr H H Ph4-iBuNHCOCH₂—Ph 2394 H H i-Pr H H Ph 4-tBuO₂CCH₂-3-I—Ph 2395 H H i-Pr HH Ph 3-I-4-PhCH₂NHCOCH₂—Ph 2396 H H i-Pr H H Ph3-I-4-(2-tetrahydrafuryl)CH₂NHCOCH₂—Ph 2397 H H i-Pr H H Ph4-cycloPrNHCOCH₂-3-I—Ph 2398 H H i-Pr H H Ph 4-cycloPentylNHCOCH₂-3-I—Ph2399 H H i-Pr H H Ph 4-cycloHexylNHCOCH₂-3-I—Ph 2400 H H i-Pr H H Ph4-cycloPrNHCOCH₂-3-F—Ph 2401 H H i-Pr H H Ph 3-Cl-4-i-PrNHCOCH₂CH₂—Ph2402 H H i-Pr H H Ph 3-Cl-4-EtNHCOCH₂CH₂—Ph 2403 H H i-Pr H H Ph3-Cl-4-EtCH(Me)NHCOCH₂CH₂—Ph 2404 H H i-Pr H H Ph 4-i-PrNHCO-3-Me—Ph2405 H H i-Pr H H Ph 4-EtNHCO-3-Me—Ph 2406 H H i-Pr H H Ph4-EtCH(Me)NHCO-3-Me—Ph 2407 H H i-Pr H H Ph 3-Cl-4-i-PrNHCH₂CH₂O—Ph 2408H H i-Pr H H Ph 3-Cl-4-EtNHCH₂CH₂O—Ph 2409 H H i-Pr H H Ph3-Cl-4-EtCH(Me)NHCH₂CH₂O—Ph 2410 H H i-Pr H Me Ph 3-Cl-4-n-PrNHCOCH₂O—Ph2411 H H i-Pr H Me Ph 3-Cl-4-i-PrNHCOCH₂O—Ph 2412 H H i-Pr H Me Ph3-Cl-4-EtNHCOCH₂O—Ph 2413 H H i-Pr H Me Ph 3-Cl-4-EtCH(Me)NHCOCH₂O—Ph2414 H H i-Pr H Me Ph 3-Cl-4-cycloPrNHCOCH₂O—Ph 2415 H H i-Pr H Me Ph3-Cl-4-cycloPentylNHCOCH₂O—Ph 2416 H H i-Pr H Et Ph3-Me-4-n-PrNHCOCH₂O—Ph 2417 H H i-Pr H Et Ph 4-i-PrNHCOCH₂O-3-Me—Ph

[0235] TABLE 20 [I-2]

Com- pound No. R¹ R² R³ R⁴ R⁵ Z R 2418 H H i-Pr H Et Ph4-EtNHCOCH₂O-3-Me—Ph 2419 H H i-Pr H Et Ph 3-Me-4-MeNHCOCH₂O—Ph 2420 H Hi-Pr H Et Ph 3-Me-4-n- BuNHCOCH₂O—Ph 2421 H H i-Pr H Et Ph4-EtCH(Me)NHCOCH₂O- 3-Me—Ph 2422 H H i-Pr H Et Ph 4-EtCOCH₂O-3-Me—Ph2423 H H i-Pr H Et Ph 4-i-BuNHCOCH₂O- 3-Me—Ph 2424 H H i-Pr H Ac Ph3-Cl-4-n-PrNHCOCH₂O—Ph 2425 H H i-Pr H Ac Ph 3-Cl-4-i-PrNHCOCH₂O—Ph 2426H H i-Pr H Ac Ph 3-Cl-4-EtNHCOCH₂O—Ph 2427 H H i-Pr H Ac Ph 3-Cl-4-EtCH(Me)NHCOCH₂O—Ph 2428 H H i-Pr H Ac Ph 3-Cl-4- cycloPrNHCOCH₂O—Ph2429 H H i-Pr H Ac Ph 3-Cl-4- cycloPentylNHCOCH₂O—Ph 2430 H H i-Pr H OHPh 3-Me-4-n- PrNHCOCH₂O—Ph 2431 H H i-Pr H OH Ph 4-i-PrNHCOCH₂O-3-Me—Ph2432 H H i-Pr H OH Ph 4-EtNHCOCH₂O-3-Me—Ph 2433 H H i-Pr H OH Ph3-Me-4-MeNHCOCH₂O—Ph 2434 H H i-Pr H OH Ph 3-Me-4-n- BuNHCOCH₂O—Ph 2435H H i-Pr H OH Ph 4-EtCH(Me)NHCOCH₂O- 3-Me—Ph 2436 H H i-Pr H OH Ph4-EtCOCH₂O-3-Me—Ph 2437 H H i-Pr H OH Ph 4-i-BuNHCOCH₂O- 3-Me—Ph 2438 HH i-Pr H OMe Ph 3-Cl-4-n-PrNHCOCH₂O—Ph 2439 H H i-Pr H OMe Ph3-Cl-4-i-PrNHCOCH₂O—Ph 2440 H H i-Pr H OMe Ph 3-Cl-4-EtNHCOCH₂O—Ph 2441H H i-Pr H OMe Ph 3-Cl-4- EtCH(Me)NHCOCH₂O—Ph 2442 H H i-Pr H OMe Ph3-Cl-4- cycloPrNHCOCH₂O—Ph 2443 H H i-Pr H OMe Ph 3-Cl-4-cycloPentylNHCOCH₂O—Ph 2444 H H i-Pr H OEt Ph 3-Me-4-n- PrNHCOCH₂O—Ph2445 H H i-Pr H OEt Ph 4-i-PrNHCOCH₂O-3-Me—Ph 2446 H H i-Pr H OEt Ph4-EtNHCOCH₂O-3-Me—Ph 2447 H H i-Pr H OEt Ph 3-Me-4-MeNHCOCH₂O—Ph 2448 HH i-Pr H OEt Ph 3-Me-4-n- BuNHCOCH₂O—Ph 2449 H H i-Pr H OEt Ph4-EtCH(Me)NHCOCH₂O- 3-Me—Ph 2450 H H i-Pr H OEt Ph 4-EtCOCH₂O-3-Me—Ph2451 H H i-Pr H OEt Ph 4-i-BuNHCOCH₂O- 3-Me—Ph 2452 H H i-Pr H Pr Ph3-Cl-4-n-PrNHCOCH₂O—Ph 2453 H H i-Pr H Pr Ph 3-Cl-4-i-PrNHCOCH₂O—Ph 2454H H i-Pr H Pr Ph 3-Cl-4-EtNHCOCH₂O—Ph 2455 H H i-Pr H Pr Ph 3-Cl-4-EtCH(Me)NHCOCH₂O—Ph 2456 H H i-Pr H Pr Ph 3-Cl-4- cycloPrNHCOCH₂O—Ph2457 H H i-Pr H Pr Ph 3-Cl-4- cycloPentylNHCOCH₂O—Ph 2458 H H i-Pr Hi-Pr Ph 3-Me-4-n- PrNHCOCH₂O—Ph 2459 H H i-Pr H i-Pr Ph4-i-PrNHCOCH₂O-3-Me—Ph 2460 H H i-Pr H i-Pr Ph 4-EtNHCOCH₂O-3-Me—Ph 2461H H i-Pr H i-Pr Ph 3-Me-4-MeNHCOCH₂O-—Ph 2462 H H i-Pr H i-Pr Ph3-Me-4-n- BuNHCOCH₂O—Ph 2463 H H i-Pr H i-Pr Ph 4-EtCH(Me)NHCOCH₂O-3-Me—Ph

[0236] TABLE 21 [I-2]

Compound No. R¹ R² R³ R⁴ R⁵ Z R 2464 H H i-Pr H H 4,5-ethylenedioxy-Ph4-nBuNHCOCH₂O—Ph 2465 H H i-Pr H H Ph 3-PhCO₂-4-nPrNHCOCH₂O—Ph 2466 H Hi-Pr H H Ph 3-cycloPrNH-4-nPrNHCOCH₂O—Ph 2467 H H i-Pr H H Ph4-nPrNHCOCH₂O-pyrimidin-5-yl 2468 H H MeSO₂NHCH₂CH₂ H H Ph4-nPrNHCOCH₂O—Ph 2469 H H MeOCH₂CH₂ H H Ph 4-nPrNHCOCH₂O—Ph 2470 H HMeO₂CCH═CH H H Ph 4-nPrNHCOCH₂O—Ph 2471 H H i-Pr H Me Ph4-nPrNHCOCH₂O—Ph 2472 H H i-Pr H nPrNHCOCH₂ Ph 4-nPrNHCOCH₂O—Ph 2473 H Hi-Pr H H₂NCOCH₂ Ph 4-nPrNHCOCH₂O—Ph 2474 H H i-Pr H MeSO₂NHCOCH₂ Ph4-nPrNHCOCH_(2O—Ph) 2475 H H i-Pr H MeO₂CCH₂ Ph 4-nPrNHCOCH₂O—Ph 2476 HH i-Pr H HOCH₂CH₂ Ph 4-nPrNHCOCH₂O—Ph

[0237] TABLE 22 [I-3]

Com- pound No. R¹ R² R³ R⁴ R⁶ Z R 3001 H H i-Pr H H Ph 2-MeO—Ph 3002 H Hi-Pr H H Ph Ph 3003 H H i-Pr H H Ph 2-NH₂—Ph 3004 H H i-Pr H H Ph 4-F—Ph3005 H H i-Pr H H Ph 4-Et₂N—Ph 3006 H H i-Pr H H Ph 4-Cl—Ph 3007 H Hi-Pr H H Ph 4-HO—Ph 3008 H H i-Pr H H Ph 3-MeO—Ph 3009 H H i-Pr H H Ph3-HO—Ph 3010 H H i-Pr H H Ph 3-NH₂—Ph 3011 H H i-Pr H H Ph 4-MeO—Ph 3012H H i-Pr H H Ph 4-Me—Ph 3013 H H i-Pr H H Ph 3-Me—Ph 3014 H H i-Pr H HPh 4-tBuO₂CCH₂O—Ph 3015 H H i-Pr H H Ph 4-HO₂CCH₂O—Ph 3016 H H i-Pr H HPh 4-tBuO₂C(CH₂)₅O—Ph 3017 H H i-Pr H H Ph 4-HO₂C(CH₂)₅O—Ph 3018 H Hi-Pr H H Ph 4-HO(CH₂)₃O—Ph 3019 H H i-Pr H H Ph 4-HO(CH₂)₂O—Ph 3020 H Hi-Pr H H Ph 4-HOC(Me)₂(CH₂)₂O—Ph 3021 H H i-Pr H H Ph 4-PhCH₂O—Ph 3022 HH i-Pr H H Ph 4-MeNHCOCH₂O—Ph 3023 H H i-Pr H H Ph 4-EtNHCOCH₂O—Ph 3024H H i-Pr H H Ph 4-nPrNHCOCH₂O—Ph 3025 H H i-Pr H H Ph 4-nBuNHCOCH₂O—Ph3026 H H i-Pr H H Ph 4- CH₂═CHCH₂NHCOCH₂O—Ph 3027 H H i-Pr H H Ph4-Me(CH₂)₉NHCOCH₂O—Ph 3028 H H i-Pr H H Ph 4-N₃(CH₂)₃O—Ph 3029 H H i-PrH H Ph 4-tBuO₂CCH(Me)O—Ph 3030 H H i-Pr H H Ph 4-nPrNHCOCH(Me)O—Ph 3031H H i-Pr H H Ph 4-F₃CSO₃—Ph 3032 H H i-Pr H H Ph 4-tBuO₂CCH═CHPh 3033 HH i-Pr H H Ph 4-nPrNHCOCH═CH—Ph 3034 H H i-Pr H H Ph4-nPrCH(Me)NHCOCH₂O—Ph 3035 H H i-Pr H H Ph 4-EtCH(Me)NHCOCH₂O—Ph 3036 HH i-Pr H H Ph 4-MeOCH₂O—Ph 3037 H H i-Pr H H Ph 4-EtCOCH₂O—Ph 3038 H Hi-Pr H H Ph 3-tBuO₂CCH₂O—Ph 3039 H H i-Pr H H Ph 3-HO₂CCH₂O—Ph 3040 H Hi-Pr H H Ph 3-nPrNHCOCH₂O—Ph 3041 H H i-Pr H H Ph 4-H₂NC(Me)₂CH₂O₂CCH₂O—Ph 3042 H H i-Pr H H Ph 4-morpholinoCOCH₂O—Ph 3043 HH i-Pr H H Ph 4-(4-Cl—Ph)—COCH₂O—Ph 3044 H H i-Pr H H Ph 4-PhCOCH₂O—Ph3045 H H i-Pr H H Ph 4-(4-pyridyl)- CH₂NHCOCH₂O— 3046 H H i-Pr H H Ph 4-H₂NCH₂CH₂NHCOCH₂O—Ph 3047 H H i-Pr H H Ph 4-Cl-3-NO₂—Ph

[0238] TABLE 23 [I-3]

Compound No. R¹ R² R³ R⁴ R⁶ Z R 3048 H H i-Pr H H Ph 4-Cl-3-F—Ph 3049 HH i-Pr H H Ph 4-Cl-3-Me—Ph 3050 H H i-Pr H H Ph 3-NH₂-4-Cl—Ph 3051 H Hi-Pr H H Ph 3-Cl-4-MeO—Ph 3052 H H i-Pr H H Ph 3-Cl-4-Me—Ph 3053 H Hi-Pr H H Ph 4-Br-3-Cl—Ph 3054 H H i-Pr H H Ph 4-Br-2-Cl—Ph 3055 H H i-PrH H Ph 4-F-3-Me—Ph 3056 H H i-Pr H H Ph 3-F-4-Me—Ph 3057 H H i-Pr H H Ph3-Br-4-HO—Ph 3058 H H i-Pr H H Ph 3-Br-4-MeO—Ph 3059 H H i-Pr H H Ph3-Br-4-F—Ph 3060 H H i-Pr H H Ph 3-F-4-PhPh 3061 H H i-Pr H H Ph4-HO-3-I—Ph 3062 H H i-Pr H H Ph 5-HO-2-I—Ph 3063 H H i-Pr H H Ph3-I-4-MeO—Ph 3064 H H i-Pr H H Ph 2-I-5-MeO—Ph 3065 H H i-Pr H H Ph4-MeO-3-Me—Ph 3066 H H i-Pr H H Ph 4-HO(CH₂)₃O-3-I—Ph 3067 H H i-Pr H HPh 4-HO(CH₂)₂O-3-I—Ph 3068 H H i-Pr H H Ph 4-HOC(Me)₂(CH₂)₂O-3-I—Ph 3069H H i-Pr H H Ph 4-tBuO₂C(CH₂)₄O-3-I—Ph 3070 H H i-Pr H H Ph3-I-4-PhCH₂O—Ph 3071 H H i-Pr H H Ph 4-H₂NCOCH₂O-3-I—Ph 3072 H H i-Pr HH Ph 3-I-4-MeNHCOCH₂O—Ph 3073 H H i-Pr H H Ph 4-EtNHCOCH₂O-3-I—Ph 3074 HH i-Pr H H Ph 3-I-4-nPrNHCOCH₂O—Ph 3075 H H i-Pr H H Ph3-I-4-iPrNHCOCH₂O—Ph 3076 H H i-Pr H H Ph 4-nBuNHCOCH₂O-3-I—Ph 3077 H Hi-Pr H H Ph 4-tBuNHCOCH₂O-3-I—Ph 3078 H H i-Pr H H Ph 4-iBuNHCOCH₂O—Ph3079 H H i-Pr H H Ph 4-tBuO₂CCH₂O-3-I—Ph 3080 H H i-Pr H H Ph3-I-4-PhCH₂NHCOCH₂O—Ph 3081 H H i-Pr H H Ph3-I-4-(2-tetrahydrofuryl)CH₂NHCOCH₂O—Ph 3082 H H i-Pr H H Ph4-cycloPrNHCOCH₂O-3-I—Ph 3083 H H i-Pr H H Ph4-cycloPentylNHCOCH₂O-3-I—Ph 3084 H H i-Pr H H Ph4-cycloHexylNHCOCH₂O-3-I—Ph 3085 H H i-Pr H H Ph4-cycloPrNHCOCH₂O-3-F—Ph 3086 H H i-Pr H H Ph 4-Me(CH₂)₉NHCOCH₂O-3-I—Ph3087 H H i-Pr H H Ph 4-HO₂CCH₂O-3-I—Ph 3088 H H i-Pr H H Ph4-N₃(CH₂)₃O-3-I—Ph 3089 H H i-Pr H H Ph 3-I-4-nPrNHCO(CH₂)₄O—Ph 3090 H Hi-Pr H H Ph 4-Et₂NCOCH₂O-3-I—Ph 3091 H H i-Pr H H Ph3-I-4-nPrN(Me)COCH₂O—Ph 3092 H H i-Pr H H Ph 3-Cl-4-nPrNHCOCH₂O—Ph 3093H H i-Pr H H Ph 3-Br-4-nPrNHCOCH₂O—Ph 3094 H H i-Pr H H Ph3-F-4-nPrNHCOCH₂O—Ph

[0239] TABLE 24 [I-3]

Compound No. R¹ R² R³ R⁴ R⁶ Z R 3095 H H i-Pr H H Ph3-Me-4-nPrNHCOCH₂O—Ph 3096 H H i-Pr H H Ph 4-EtNHCOCH₂O-3-F—Ph 3097 H Hi-Pr H H Ph 3-I-4-iPrNHCOC(Me)₂CH₂O—Ph 3098 H H i-Pr H H Ph3-Br-4-CH₂═CHCH₂NHCOCH₂O—Ph 3099 H H i-Pr H H Ph 4-iBuNHCOCH₂O-3-F—Ph3100 H H i-Pr H H Ph 3-tBuO₂CCH═CH-4-nPrNHCOCH₂O—Ph 3101 H H i-Pr H H Ph3-HO₂CCH═CH-4-nPrNHCOCH₂O—Ph 3102 H H i-Pr H H Ph3-I-4-MeOCH₂CH₂NHCOCH₂O—Ph 3103 H H i-Pr H H Ph 3-F-4-HO—Ph 3104 H Hi-Pr H H Ph 3-F-4-MeO—Ph 3105 H H i-Pr H H Ph 3,4-methylenedioxyPh 3106H H i-Pr H H Ph 3,4-ethylenedioxyPh 3107 H H i-Pr H H Ph 3,4-Cl₂—Ph 3108H H i-Pr H H Ph 3,4-Me₂—Ph 3109 H H i-Pr H H Ph 3,4-F₂—Ph 3110 H H i-PrH H Ph 3,4-(MeO)₂—Ph 3111 H H i-Pr H H Ph 3,5-(MeO)₂—Ph 3112 H H i-Pr HH Ph 3,5-Me₂—Ph 3113 H H i-Pr H H Ph 3,5-I₂-4-HO—Ph 3114 H H i-Pr H H Ph2,4-I₂-5-HO—Ph 3115 H H i-Pr H H Ph 3,5-I₂-4-MeO—Ph 3116 H H i-Pr H H Ph2,4-I₂-5-MeO—Ph 3117 H H i-Pr H H Ph 2,4,6-Me₃—Ph 3118 H H i-Pr H H Ph4-HO(CH₂)₃O-3,5-I₂Ph 3119 H H i-Pr H H Ph 3,5-I₂-4-nPrNHCOCH₂O—Ph 3120 HH i-Pr H H Ph 2-thienyl 3121 H H i-Pr H H Ph 2-furyl 3122 H H i-Pr H HPh 3-pyridyl 3123 H H i-Pr H H Ph 2-naphthyl 3124 H H i-Pr H H Ph5-F-1-naphthyl 3125 H H i-Pr H H Ph dibenzothiophene-2-yl 3126 6-F Hi-Pr H H Ph Ph 3127 7-F H i-Pr H H Ph Ph 3128 8-F H i-Pr H H Ph Ph 31299-F H i-Pr H H Ph Ph 3130 6-MeO H i-Pr H H Ph Ph 3131 9-MeO H i-Pr H HPh Ph 3132 6-OH H i-Pr H H Ph Ph 3133 9-OH H i-Pr H H Ph Ph 3134 7-NO₂ Hi-Pr H H Ph Ph 3135 8-NO₂ H i-Pr H H Ph Ph 3136 9-NO₂ H i-Pr H H Ph Ph3137 6-NHPh H i-Pr H H Ph Ph 3138 7-Me₂N H i-Pr H H Ph Ph 3139 7-Me Hi-Pr H H Ph Ph 3140 8-Me H i-Pr H H Ph Ph 3141 7-t-Bu H i-Pr H H Ph Ph

[0240] TABLE 25 [I-3]

Com- pound No. R¹ R² R³ R⁴ R⁶ Z R 3142 8-t-Bu H i-Pr H H Ph Ph 3143 7-BrH i-Pr H H Ph Ph 3144 8-Br H i-Pr H H Ph Ph 3145 7-Cl H i-Pr H H Ph Ph3146 8-Cl H i-Pr H H Ph Ph 3147 7-Cl 8-Cl i-Pr H H Ph Ph 3148 6-Cl 9-Cli-Pr H H Ph Ph 3149 6-OH 9-I i-Pr H H Ph Ph 3150 H H i-Pr H H 1,2- Phnaphthyl 3151 H H i-Pr H H 2,3- Ph naphthyl 3152 H H i-Pr H H cyclo- Phhexenyl 3153 H H D-Leucine H H Ph Ph 3154 H H L-Leucine H H Ph Ph 3155 HH D-NorLeucine H H Ph Ph 3156 H H L-NorLeucine H H Ph Ph 3157 H HD-AlloLeucine H H Ph Ph 3158 H H L-AlloLeucine H H Ph Ph 3159 H HD-NorValine H H Ph Ph 3160 H H L-NorValine H H Ph Ph 3161 H H D-AlanineH H Ph Ph 3162 H H L-Alanine H H Ph Ph 3163 H H D-Arginine H H Ph Ph3164 H H L-Arginine H H Ph Ph 3165 H H D-Asparagine H H Ph Ph 3166 H HL-Asparagine H H Ph Ph 3167 H H D-Glutamic H H Ph Ph Acid 3168 H HL-Glutamic H H Ph Ph Acid 3169 H H D-Glutamine H H Ph Ph 3170 H HL-Glutamine H H Ph Ph 3171 H H D-Histidine H H Ph Ph 3172 H HL-Histidine H H Ph Ph 3173 H H D-Methionine H H Ph Ph 3174 H HL-Methionine H H Ph Ph 3175 H H D-Tryptophan H H Ph Ph 3176 H HL-Tryptophan H H Ph Ph 3177 H H D-Tyrosine H H Ph Ph 3178 H H L-TyrosineH H Ph Ph 3179 H H Homo H H Ph Ph Phenylalar 3180 H H Homo H H Ph PhPhenylalar 3181 H H D-Leucine H H Ph 4- Cl—Ph 3182 H H L-Leucine H H Ph4- Cl—Ph 3183 H H D-NorLeucine H H Ph 4- Cl—Ph 3184 H H L-NorLeucine H HPh 4- Cl—Ph 3185 H H D-AlloLeucine H H Ph 4- Cl—Ph 3186 H HL-AlloLeucine H H Ph 4- Cl—Ph 3187 H H D-NorValine H H Ph 4- Cl—Ph

[0241] TABLE 26 [I-3]

Compound No. R¹ R² R³ R⁴ R⁶ Z R 3188 H H L-NorValine H H Ph 4-Cl—Ph 3189H H D-Alanine H H Ph 4-Cl—Ph 3190 H H L-Alanine H H Ph 4-Cl—Ph 3191 H HD-Arginine H H Ph 4-Cl—Ph 3192 H H L-Arginine H H Ph 4-Cl—Ph 3193 H HD-Asparagine H H Ph 4-Cl—Ph 3194 H H L-Asparagine H H Ph 4-Cl—Ph 3195 HH D-Glutamic Acid H H Ph 4-Cl—Ph 3196 H H L-Glutamic Acid H H Ph 4-Cl—Ph3197 H H D-Glutamine H H Ph 4-Cl—Ph 3198 H H L-Glutamine H H Ph 4-Cl—Ph3199 H H D-Histidine H H Ph 4-Cl—Ph 3200 H H L-Histidine H H Ph 4-Cl—Ph3201 H H D-Methionine H H Ph 4-Cl—Ph 3202 H H L-Methionine H H Ph4-Cl—Ph 3203 H H D-Tryptophan H H Ph 4-Cl—Ph 3204 H H L-Tryptophan H HPh 4-Cl—Ph 3205 H H D-Tyrosine H H Ph 4-Cl—Ph 3206 H H L-Tyrosine H H Ph4-Cl—Ph 3207 H H D-Homo Phenylalanine H H Ph 4-Cl—Ph 3208 H H L-HomoPhenylalanine H H Ph 4-Cl—Ph 3209 H H t-Bu H H Ph Ph 3210 H H(CH₃)₂(OH)C H H Ph Ph 3211 H H CH₃(MeO)CH H H Ph Ph 3212 H H 4-HO—Ph H HPh Ph 3213 H H 4-HO-3-I—Ph H H Ph Ph 3214 H H 4-HO-3,5-I₂—Ph H H Ph Ph3215 H H 4-HO-3-I—PhCH₂ H H Ph Ph 3216 H H 4-HO-3,5-I₂—PhCH₂ H H Ph Ph3217 H H 1-naphthylmethyl H H Ph Ph 3218 H H 4-F—PhCH₂ H H Ph Ph 3219 HH 1-naphthylmethyl H H Ph 4-Cl—Ph 3220 H H 4-F—PhCH₂ H H Ph 4-Cl—Ph 3221H H i-Pr Me H Ph 4-Cl—Ph 3222 H H Me Me H Ph Ph 3223 H H (Combined withR⁴)CH₂═ — H Ph Ph 3224 H H (Combined with R⁴)MeCH═ — H Ph Ph 3225 H H(Combined with R⁴)(CH₂)₄ — H Ph Ph 3226 H H i-Pr H H Ph4-n-PrNHCOCH₂CH₂O—Ph 3227 H H i-Pr H H Ph 4-i-PrNHCOCH₂CH₂O—Ph 3228 H Hi-Pr H H Ph 4-EtNHCOCH₂CH₂O—Ph 3229 H H i-Pr H H Ph4-EtCH(Me)NHCOCH₂CH₂O—Ph 3230 H H i-Pr H H Ph 3-Cl-4-i-PrNHCOCH₂O—Ph3231 H H i-Pr H H Ph 3-Cl-4-EtNHCOCH₂O—Ph 3232 H H i-Pr H H Ph3-Cl-4-EtCH(Me)NHCOCH₂O—Ph 3233 H H i-Pr H H Ph 4-i-PrNHCOCH₂O-3-Me—Ph

[0242] TABLE 27 [I-3]

Compound No. R¹ R² R³ R⁴ R⁶ Z R 3234 H H i-Pr H H Ph4-EtNHCOCH₂O-3-Me—Ph 3235 H H i-Pr H H Ph 4-EtCH(Me)NHCOCH₂O-3-Me—Ph3236 H H i-Pr H H Ph 4-cycloPrNHCOCH₂CH₂O—Ph 3237 H H i-Pr H H Ph4-cycloPentylNHCOCH₂CH₂O—Ph 3238 H H i-Pr H H Ph3-I-4-n-PrNHCOCH₂CH₂O—Ph 3239 H H i-Pr H H Ph 3-I-4-i-PrNHCOCH₂CH₂O—Ph3240 H H i-Pr H H Ph 4-EtNHCOCH₂CH₂O-3-I—Ph 3241 H H i-Pr H H Ph4-EtCH(Me)NHCOCH₂CH₂O-3-I—Ph 3242 H H i-Pr H H Ph 4-EtCOCH₂CH₂O-3-I—Ph3243 H H i-Pr H H Ph 4-cycloPrNHCOCH₂CH₂O-3-I—Ph 3244 H H i-Pr H H Ph4-cycloPentylNHCOCH₂CH₂O-3-I—Ph 3245 H H i-Pr H H Ph3-F-4-n-PrNHCOCH₂CH₂O—Ph 3246 H H i-Pr H H Ph 3-F-4-i-PrNHCOCH₂CH₂O—Ph3247 H H i-Pr H H Ph 4-EtNHCOCH₂CH₂O-3-F—Ph 3248 H H i-Pr H H Ph4-EtCH(Me)NHCOCH₂CH₂O-3-F—Ph 3249 H H i-Pr H H Ph 4-EtCOCH₂CH₂O-3-F—Ph3250 H H i-Pr H H Ph 3-F-4-i-BuNHCOCH₂CH₂O—Ph 3251 H H i-Pr H H Ph4-cycloPrNHCOCH₂CH₂O-3-F—Ph 3252 H H i-Pr H H Ph3-Br-4-n-PrNHCOCH₂CH₂O—Ph 3253 H H i-Pr H H Ph 3-Br-4-i-PrNHCOCH₂CH₂O—Ph3254 H H i-Pr H H Ph 3-Br-4-EtNHCOCH₂CH₂O—Ph 3255 H H i-Pr H H Ph3-Br-4-i-BuNHCOCH₂CH₂O—Ph 3256 H H i-Pr H H Ph 3-Cl-4-n-PrNHCOCH₂CH₂O—Ph3257 H H i-Pr H H Ph 3-Cl-4-i-PrNHCOCH₂CH₂O—Ph 3258 H H i-Pr H H Ph3-Cl-4-EtNHCOCH₂CH₂O—Ph 3259 H H i-Pr H H Ph3-Cl-4-EtCH(Me)NHCOCH₂CH₂O—Ph 3260 H H i-Pr H H Ph3-Cl-4-cycloPrNHCOCH₂CH₂O—Ph 3261 H H i-Pr H H Ph3-Cl-4-cycloPentylNHCOCH₂CH₂O—Ph 3262 H H i-Pr H H Ph3-Me-4-n-PrNHCOCH₂CH₂O—Ph 3263 H H i-Pr H H Ph 4-i-PrNHCOCH₂CH₂O-3-Me—Ph3264 H H i-Pr H H Ph 4-EtNHCOCH₂CH₂O-3-Me—Ph 3265 H H i-Pr H H Ph3-Me-4-MeNHCOCH₂CH₂O—Ph 3266 H H i-Pr H H Ph 3-Me-4-n-BuNHCOCH₂CH₂O—Ph3267 H H i-Pr H H Ph 4-EtCH(Me)NHCOCH₂CH₂O-3-Me—Ph 3268 H H i-Pr H H Ph4-EtCOCH₂CH₂O-3-Me—Ph 3269 H H i-Pr H H Ph 4-i-BuNHCOCH₂CH₂O-3-Me—Ph3270 H H i-Pr H H Ph 3-Me-4-t-BuNHCOCH₂CH₂O—Ph 3271 H H i-Pr H H Ph4-cycloPrNHCOCH₂CH₂O-3-Me—Ph 3272 H H i-Pr H H Ph4-cycloPentylNHCOCH₂CH₂O-3-Me—Ph 3273 H H Me H H Ph3-Cl-4-n-PrNHCOCH₂O—Ph 3274 H H Me H H Ph 3-Cl-4-i-PrNHCOCH₂O—Ph 3275 HH Me H H Ph 3-Cl-4-EtNHCOCH₂O—Ph 3276 H H Me H H Ph3-Cl-4-EtCH(Me)NHCOCH₂O—Ph 3277 H H Me H H Ph 3-Cl-4-cycloPrNHCOCH₂O—Ph3278 H H Me H H Ph 3-Cl-4-cycloPentylNHCOCH₂O—Ph 3279 H H Et H H Ph3-Me-4-n-PrNHCOCH₂O—Ph

[0243] TABLE 28 [I-3]

Compound No. R¹ R² R³ R⁴ R⁶ Z R 3280 H H Et H H Ph4-i-PrNHCOCH₂O-3-Me—Ph 3281 H H Et H H Ph 4-EtNHCOCH₂O-3-Me—Ph 3282 H HEt H H Ph 3-Me-4-MeNHCOCH₂O—Ph 3283 H H Et H H Ph 3-Me-4-n-BuNHCOCH₂O—Ph3284 H H Et H H Ph 4-EtCH(Me)NHCOCH₂O-3-Me—Ph 3285 H H Et H H Ph4-EtCOCH₂O-3-Me—Ph 3286 H H Et H H Ph 4-i-BuNHCOCH₂O-3-Me—Ph 3287 H H PrH H Ph 3-Cl-4-n-PrNHCOCH₂O—Ph 3288 H H Pr H H Ph 3-Cl-4-i-PrNHCOCH₂O—Ph3289 H H Pr H H Ph 3-Cl-4-EtNHCOCH₂O—Ph 3290 H H Pr H H Ph3-Cl-4-EtCH(Me)NHCOCH₂O—Ph 3291 H H Pr H H Ph 3-Cl-4-cycloPrNHCOCH₂O—Ph3292 H H Pr H H Ph 3-Cl-4-cycloPentylNHCOCH₂O—Ph 3293 H H Bu H H Ph3-Me-4-n-PrNHCOCH₂O—Ph 3294 H H Bu H H Ph 4-i-PrNHCOCH₂O-3-Me—Ph 3295 HH Bu H H Ph 4-EtNHCOCH₂O-3-Me—Ph 3296 H H Bu H H Ph 3-Me-4-MeNHCOCH₂O—Ph3297 H H Bu H H Ph 3-Me-4-n-BuNHCOCH₂O—Ph 3298 H H Bu H H Ph4-EtCH(Me)NHCOCH₂O-3-Me—Ph 3299 H H Bu H H Ph 4-EtCOCH₂O-3-Me—Ph 3300 HH Bu H H Ph 4-i-BuNHCOCH₂O-3-Me—Ph 3301 H H i-Bu H H Ph3-Cl-4-n-PrNHCOCH₂O—Ph 3302 H H i-Bu H H Ph 3-Cl-4-HPrNHCOCH₂O—Ph 3303 HH i-Bu H H Ph 3-Cl-4-EtNHCOCH₂O—Ph 3304 H H i-Bu H H Ph3-Cl-4-EtCH(Me)NHCOCH₂O—Ph 3305 H H i-Bu H H Ph3-Cl-4-cycloPrNHCOCH₂O—Ph 3306 H H i-Bu H H Ph3-Cl-4-cycloPentylNHCOCH₂O—Ph 3307 H H t-Bu H H Ph3-Me-4-n-PrNHCOCH₂O—Ph 3308 H H t-Bu H H Ph 4-i-PrNHCOCH₂O-3-Me—Ph 3309H H t-Bu H H Ph 4-EtNHCOCH₂O-3-Me—Ph 3310 H H t-Bu H H Ph3-Me-4-MeNHCOCH₂O—Ph 3311 H H PhCH₂ H H Ph 3-Me-4-n-BuNHCOCH₂O—Ph 3312 HH PhCH₂ H H Ph 4-EtCH(Me)NHCOCH₂O-3-Me—Ph 3313 H H PhCH₂ H H Ph4-EtCOCH₂O-3-Me—Ph 3314 H H PhCH₂ H H Ph 4-i-BuNHCOCH₂O-3-Me—Ph 3315 H Hi-Pr Me H Ph 3-Cl-4-n-PrNHCOCH₂O—Ph 3316 H H i-Pr Me H Ph3-Cl-4-i-PrNHCOCH₂O—Ph 3317 H H i-Pr Me H Ph 3-Cl-4-EtNHCOCH₂O—Ph 3318 HH i-Pr Me H Ph 3-Cl-4-EtCH(Me)NHCOCH₂O—Ph 3319 H H i-Pr Me H Ph3-Cl-4-cycloPrNHCOCH₂O—Ph 3320 H H i-Pr Me H Ph3-Cl-4-cycloPentylNHCOCH₂O—Ph 3321 H H i-Pr H H 2,3-Pyridyl3-Me-4-n-PrNHCOCH₂O—Ph 3322 H H i-Pr H H 2,3-Pyridyl4-i-PrNHCOCH₂O-3-Me—Ph 3323 H H i-Pr H H 2,3-Pyridyl4-EtNHCOCH₂O-3-Me—Ph 3324 H H i-Pr H H 2,3-Pyridyl 3-Me-4-MeNHCOCH₂O—Ph3325 H H i-Pr H H 2,3-Pyridyl 3-Me-4-n-BuNHCOCH₂O—Ph

[0244] TABLE 29 [I-3]

Compound No R¹ R² R³ R⁴ R⁶ Z R 3326 H H i-Pr H H 2,3-Pyridyl4-EtCH(Me)NHCOCH₂O-3-Me—Ph 3327 H H i-Pr H H 2,3-Pyridyl4-EtCOCH₂O-3-Me—Ph 3328 H H i-Pr H H 2,3-Pyridyl 4-i-BuNHCOCH₂O-3-Me—Ph3329 H H i-Pr H H 2,3-Pyridyl 3-Cl-4-n-PrNHCOCH₂O—Ph 3330 H H i-Pr H H3,4-Pyridyl 3-Cl-4-i-PrNHCOCH₂O—Ph 3331 H H i-Pr H H 3,4-Pyridyl3-Cl-4-EtNHCOCH₂O—Ph 3332 H H i-Pr H H 3,4-Pyridyl3-Cl-4-EtCH(Me)NHCOCH₂O—Ph 3333 H H i-Pr H H 3,4-Pyridyl3-Cl-4-cycloPrNHCOCH₂O—Ph 3334 H H i-Pr H H 3,4-Pyridyl3-Cl-4-cycloPentylNHCOCH₂O—Ph 3335 H H i-Pr H H Ph4-F-5-n-PrNHCOCH₂O-(2-pyridyl) 3336 H H i-Pr H H Ph4-F-5-i-PrNHCOCH₂₂O-(2-pyridyl) 3337 H H i-Pr H H Ph4-EtNHCOCH₂O-3-F-(2-pyridyl) 3338 H H i-Pr H H Ph4-EtCH(Me)NHCOCH₂O-3-F-(2-pyridyl) 3339 H H i-Pr H H Ph4-EtCOCH₂O-3-F-(2-pyridyl) 3340 H H i-Pr H H Ph3-F-4-i-BuNHCOCH₂O-(2-pyridyl) 3341 H H i-Pr H H Ph4-cycloPrNHCOCH₂O-3-F-(2-pyridyl) 3342 H H i-Pr H H Ph5-I-6-n-PrNHCOCH₂O-(3-pyridyl) 3343 H H i-Pr H H Ph5-I-6-i-PrNHCOCH₂O-(3-pyridyl) 3344 H H i-Pr H H Ph6-EtNHCOCH₂O-5-I-(3-pyridyl) 3345 H H i-Pr H H Ph6-EtCH(Me)NHCOCH₂O-5-I-(3-pyridyl) 3346 H H i-Pr H H Ph6-EtCOCH₂O-5-I-(3-pyridyl) 3347 H H i-Pr H H Ph6-cycloPrNHCOCH₂O-5-H(3-pyridyl) 3348 H H i-Pr H H Ph3-NO₂-4-n-PrNHCOCH₂O—Ph 3349 H H i-Pr H H Ph 3-NO₂-4-i-PrNHCOCH₂O—Ph3350 H H i-Pr H H Ph 4-EtNHCOCH₂O-3-NO₂—Ph 3351 H H i-Pr H H Ph4-EtCH(Me)NHCOCH₂O-3-NO₂—Ph 3352 H H i-Pr H H Ph 4-EtCOCH₂O-3-NO₂—Ph3353 H H i-Pr H H Ph 4-i-BuNHCOCH₂O-3-NO₂—Ph 3354 H H i-Pr H H Ph4-cycloPrNHCOCH₂O-3-NO₂—Ph 3355 H H i-Pr H H Ph 3-MeO-4-n-PrNHCOCH₂O—Ph3356 H H i-Pr H H Ph 3-MeO-4-i-PrNHCOCH₂O—Ph 3357 H H i-Pr H H Ph4-EtNHCOCH₂O-3-MeO—Ph 3358 H H i-Pr H H Ph 4-EtCH(Me)NHCOCH₂O-3-MeO—Ph3359 H H i-Pr H H Ph 4-EtCOCH₂O-3-MeO—Ph 3360 H H i-Pr H H Ph3-MeO-4-i-BuNHCOCH₂O—Ph 3361 H H i-Pr H H Ph 4-cycloPrNHCOCH₂O-3-MeO—Ph3362 H H i-Pr H H Ph 3-HO-4-n-PrNHCOCH₂O—Ph 3363 H H i-Pr H H Ph3-HO-4-i-PrNHCOCH₂O—Ph 3364 H H i-Pr H H Ph 4-EtNHCOCH₂O-3-HO—Ph 3365 HH i-Pr H H Ph 4-EtCH(Me)NHCOCH₂O-3-HO—Ph 3366 H H i-Pr H H Ph4-EtCOCH₂O-3-HO—Ph 3367 H H i-Pr H H Ph 3-HO-4-i-BuNHCOCH₂O—Ph 3368 H Hi-Pr H H Ph 4-cycloPrNHCOCH₂O-3-HO—Ph 3369 H H i-Pr H H Ph3-H₂NCH₂CH₂NHCOCH₂O—Ph 3370 H H i-Pr H H Ph 2-H₂NCH₂CH₂NHCOCH₂O—Ph 3371H H i-Pr H H Ph 4-MeNHCH₂CH₂NHCOCH₂O—Ph

[0245] TABLE 30 [I-3]

Compound No. R¹ R² R³ R⁶ Z R 3372 H H i-Pr H H Ph3-MeNHCH₂CH₂NHCOCH₂O—Ph 3373 H H i-Pr H H Ph 2-MeNHCH₂CH₂NHCOCH₂O—Ph3374 H H i-Pr H H Ph 4-Me₂NCH₂CH₂NHCOCH₂O—Ph 3375 H H i-Pr H H Ph3-Me₂NCH₂CH₂NHCOH₂O—Ph 3376 H H i-Pr H H Ph 2-Me₂NCH₂CH₂NHCOCH₂O—Ph 3377H H i-Pr H H Ph 4-H₂NCH₂CH₂NHCOCH₂O-3-Cl—Ph 3378 H H i-Pr H H Ph3-H₂NCH₂CH₂NHCOCH₂O-4-Cl—Ph 3379 H H i-Pr H H Ph2-H₂NCH₂CH₂NHCOCH₂O-4-Cl—Ph 3380 H H i-Pr H H Ph4-MeNHCH₂CH₂NHCOCH₂O-3-Me—Ph 3381 H H i-Pr H H Ph3-MeNHCH₂CH₂NHCOCH₂O-4-Me—Ph 3382 H H i-Pr H H Ph2-MeNHCH₂CH₂NHCOCH₂O-4-MePh 3383 H H i-Pr H H Ph4-Me₂NCH₂CH₂NHCOCH₂O-3-F—Ph 3384 H H i-Pr H H Ph3-Me₂NCH₂CH₂NHCOCH₂O-4-F—Ph 3385 H H i-Pr H H Ph2-Me₂NCH₂CH₂NHCOCH₂O-4-F—Ph 3386 H H i-Pr H H Ph 4-H₂NCOCH₂-3-I—Ph 3387H H i-Pr H H Ph 3-I-4-MeNHCOCH₂—Ph 3388 H H i-Pr H H Ph4-EtNHCOCH₂-3-I—Ph 3389 H H i-Pr H H Ph 3-I-4-nPrNHCOCH₂—Ph 3390 H Hi-Pr H H Ph 3-I-4-iPrNHCOCH₂—Ph 3391 H H i-Pr H H Ph 4-nBuNHCOCH₂-3-I—Ph3392 H H i-Pr H H Ph 4-tBuNHCOCH₂-3-I—Ph 3393 H H i-Pr H H Ph4-iBuNHCOCH₂—Ph 3394 H H i-Pr H H Ph 4-tBuO₂CCH₂-3-I—Ph 3395 H H i-Pr HH Ph 3-I-4-PhCH₂NHCOCH₂—Ph 3396 H H i-Pr H H Ph3-I-4-(2-tetrahydrofuryl)CH₂NHCOCH₂—Ph 3397 H H i-Pr H H Ph4-cycloPrNHCOCH₂-3-I—Ph 3398 H H i-Pr H H Ph 4-cycloPentylNHCOCH₂-3-I—Ph3399 H H i-Pr H H Ph 4-cycloHexylNHCOCH₂-3-I—Ph 3400 H H i-Pr H H Ph4-cycloPrNHCOCH₂-3-F—Ph 3401 H H i-Pr H H Ph 3-Cl-4-i-PrNHCOCH₂CH₂—Ph3402 H H i-Pr H H Ph 3-Cl-4-EtNHCOCH₂CH₂—Ph 3403 H H i-Pr H H Ph3-Cl-4-EtCH(Me)NHCOCH₂CH₂—Ph 3404 H H i-Pr H H Ph 4-i-PrNHCO-3-Me—Ph3405 H H i-Pr H H Ph 4-EtNHCO-3-Me—Ph 3406 H H i-Pr H H Ph4-EtCH(Me)NHCO-3-Me—Ph 3407 H H i-Pr H H Ph 3-Cl-4-i-PrNHCH₂CH₂O—Ph 3408H H i-Pr H H Ph 3-Cl-4-EtNHCH₂CH₂O—Ph 3409 H H i-Pr H H Ph3-Cl-4-EtCH(Me)NHCH₂CH₂O—Ph 3410 H H i-Pr H Me Ph 3-Cl-4-n-PrNHCOCH₂O—Ph3411 H H i-Pr H Me Ph 3-Cl-4-i-PrNHCOCH₂O—Ph 3412 H H i-Pr H Me Ph3-Cl-4-EtNHCOCH₂O—Ph 3413 H H i-Pr H Me Ph 3-Cl-4-EtCH(Me)NHCOCH₂O—Ph3414 H H i-Pr H Me Ph 3-Cl-4-cycloPrNHCOCH₂O—Ph 3415 H H i-Pr H Me Ph3-Cl-4-cycloPentylNHCOCH₂O—Ph 3416 H H i-Pr H Et Ph3-Me-4-n-PrNHCOCH₂O—Ph 3417 H H i-Pr H Et Ph 4-i-PrNHCOCH₂O-3-Me—Ph

[0246] TABLE 31 [I-3]

Com- pound No. R¹ R² R³ R⁴ R⁶ Z R 3418 H H i-Pr H Et Ph4-EtNHCOCH₂O-3-Me—Ph 3419 H H i-Pr H Et Ph 3-Me-4-MeNHCOCH₂O—Ph 3420 H Hi-Pr H Et Ph 3-Me-4-n- BuNHCOCH₂O—Ph 3421 H H i-Pr H Et Ph4-EtCH(Me)NHCOCH₂O- 3-Me—Ph 3422 H H i-Pr H Et Ph 4-EtCOCH₂O-3-Me—Ph3423 H H i-Pr H Et Ph 4-i-BuNHCOCH₂O- 3-Me—Ph 3424 H H i-Pr H Ac Ph3-Cl-4-n-PrNHCOCH₂O—Ph 3425 H H i-Pr H Ac Ph 3-Cl-4-i-PrNHCOCH₂O—Ph 3426H H i-Pr H Ac Ph 3-Cl-4-EtNHCOCH₂O—Ph 3427 H H i-Pr H Ac Ph 3-Cl-4-EtCH(Me)NHCOCH₂O—Ph 3428 H H i-Pr H Ac Ph 3-Cl-4- cycloPrNHCOCH₂O—Ph3429 H H i-Pr H Ac Ph 3-Cl-4- cycloPentylNHCOCH₂O—Ph 3430 H H i-Pr H OHPh 3-Me-4-n- PrNHCOCH₂O—Ph 3431 H H i-Pr H OH Ph 4-i-PrNHCOCH₂O-3-Me—Ph3432 H H i-Pr H OH Ph 4-EtNHCOCH₂O-3-Me—Ph 3433 H H i-Pr H OH Ph3-Me-4-MeNHCOCH₂O—Ph 3434 H H i-Pr H OH Ph 3-Me-4-n- BuNHCOCH₂O—Ph 3435H H i-Pr H OH Ph 4-EtCH(Me)NHCOCH₂O- 3-Me—Ph 3436 H H i-Pr H OH Ph4-EtCOCH₂O-3-Me—Ph 3437 H H i-Pr H OH Ph 4-i-BuNHCOCH₂O- 3-Me—Ph 3438 HH i-Pr H OMe Ph 3-Cl-4-n-PrNHCOCH₂O—Ph 3439 H H i-Pr H OMe Ph3-Cl-4-i-PrNHCOCH₂O—Ph 3440 H H i-Pr H OMe Ph 3-Cl-4- EtNHCOCH₂O—Ph 3441H H i-Pr H OMe Ph 3-Cl-4- EtCH(Me)NHCOCH₂O—Ph 3442 H H i-Pr H OMe Ph3-Cl-4- cycloPrNHCOCH₂O—Ph 3443 H H i-Pr H OMe Ph 3-Cl-4-cycloPentylNHCOCH₂O—Ph 3444 H H i-Pr H OEt Ph 3-Me-4-n- PrNHCOCH₂O—Ph3445 H H i-Pr H OEt Ph 4-i-PrNHCOCH₂O-3-Me—Ph 3446 H H i-Pr H OEt Ph4-EtNHCOCH₂O-3-Me—Ph 3447 H H i-Pr H OEt Ph 3-Me-4-MeNHCOCH₂O—Ph 3448 HH i-Pr H OEt Ph 3-Me-4-n- BuNHCOCH₂O—Ph 3449 H H i-Pr H OEt Ph4-EtCH(Me)NHCOCH₂O- 3-Me—Ph 3450 H H i-Pr H OEt Ph 4-EtCOCH₂O-3-Me—Ph3451 H H i-Pr H OEt Ph 4-i-BuNHCOCH₂O- 3-Me—Ph 3452 H H i-Pr H Pr Ph3-Cl-4-n-PrNHCOCH₂O—Ph 3453 H H i-Pr H Pr Ph 3-Cl-4-i-PrNHCOCH₂O—Ph 3454H H i-Pr H Pr Ph 3-Cl-4-EtNHCOCH₂O—Ph 3455 H H i-Pr H Pr Ph 3-Cl-4-EtCH(Me)NHCOCH₂O—Ph 3456 H H i-Pr H Pr Ph 3-Cl-4- cycloPrNHCOCH₂O—Ph3457 H H i-Pr H Pr Ph 3-Cl-4- cycloPentylNHCOCH₂O—Ph 3458 H H i-Pr Hi-Pr Ph 3-Me-4-n- PrNHCOCH₂O—Ph 3459 H H i-Pr H i-Pr Ph4-i-PrNHCOCH₂O-3-Me—Ph 3460 H H i-Pr H i-Pr Ph 4-EtNHCOCH₂O-3-Me—Ph 3461H H i-Pr H i-Pr Ph 3-Me-4-MeNHCOCH₂O—Ph 3462 H H i-Pr H i-Pr Ph3-Me-4-n- BuNHCOCH₂O—Ph 3463 H H i-Pr H i-Pr Ph 4-EtCH(Me)NHCOCH₂O-3-Me—Ph

[0247] TABLE 32 [I-3]

Compound No. R¹ R² R³ R⁴ R⁶ Z R 3464 H H i-Pr H H pyrimidin-4,5-yl4-nBuNHCOCH₂O—Ph 3465 H H i-Pr H H 5,6-benzimizazolyl 4-PrNHCOCH₂O—Ph3466 H H i-Pr H H Ph 3-cycloPrO-4-nPrNHCOCH₂O—Ph 3467 H H i-Pr H H Ph3-PhSO₂NHCH₂NHCO-4-nPrNHCOCH₂O—Ph 3468 H H i-Pr H H Ph3-MeNHSO₂-4-nPrNHCOCH₂O—Ph 3469 H H PhNHCOCH₂CH₂ H H Ph 4-nPrNHCOCH₂O—Ph3470 H H MeCONHCH₂CH₂ H H Ph 4-nPrNHCOCH₂O—Ph 3471 H H4-PhNHSO₂-pyrazin-2,5-y H H Ph 4-nPrNHCOCH₂O—Ph 3472 H H i-Pr H H Ph3-Cl-4-HO—Ph 3473 H H i-Pr H H Ph 4-HO-3-MePh 3474 H H i-Pr H H Ph4-HO₂CCH₂O-3-Me—Ph 3475 H H i-Pr H H Ph 3,5-Cl₂-4-nPrNHCOCH₂O—Ph 3476 HH i-Pr H H Ph 3-Me-4-nPrNHCSCH₂O—Ph 3477 H H i-Pr H H Ph3,5-Cl₂-4-nPrNHCSCH₂O—Ph 3478 H H i-Pr H H Ph 4-nPentylNHCOCH₂O—Ph 3479H H i-Pr H Me Ph 4-MeO—Ph 3480 H H i-Pr H Me Ph 4-HO—Ph 3481 H H i-Pr HMe Ph 4-nPrNHCOCH₂O—Ph 3482 H H i-Pr H Br Ph 4-nPrNHCOCH₂O—Ph 3483 H Hi-Pr H nPrNHCOCH₂ Ph 4-nPrNHCOCH₂O—Ph 3484 H H i-Pr H H₂NCOCH₂ Ph4-nPrNHCOCH₂O—Ph 3485 H H i-Pr H MeSO₂NHCH₂CH₂ Ph 4-nPrNHCOCH₂O—Ph 3486H H i-Pr H MeO₂CCH₂ Ph 4-nPrNHCOCH₂O—Ph 3487 H H i-Pr H HOCH₂CH₂ Ph4-nPrNHCOCH₂O—Ph

[0248] TABLE 33 [I-3b]

Compound No. R¹ R² R³ R⁴ R⁶ Z R 3488 H H i-Pr H H Ph3,5-Cl₂-4-nPrNHCOCH₂O—Ph 3489 H H i-Pr H H Ph 3,5-Cl₂-4-nPrNHCSCH₂O—Ph3490 H H i-Pr H H Ph 3-Me-4-nPrNHCOCH₂O—Ph 3491 H H i-Pr H H Ph3-Cl-4-nPrNHCOCH₂O—Ph 3492 H H i-Pr H H pyrimidin-4,5-yl4-nBuNHCOCH₂O—Ph 3493 H H i-Pr H H 5,6-benzimizazolyl 4-PrNHCOCH₂O—Ph3494 H H i-Pr H H Ph 3-MeSO-4-nPrNHCOCH₂O—Ph 3495 Et₂N H i-Pr H H Ph4-nPrNHCOCH₂O—Ph 3496 Ph H i-Pr H H Ph 4-nPrNHCOCH₂O—Ph 3497 H HMeSO₂CH₂CH₂ H H Ph 4-nPrNHCOCH₂O—Ph 3498 H H PhNHSO₃CH₂—Ph H H Ph4-nPrNHCOCH₂O—Ph

[0249] TABLE 34 [I-3c]

Compound No. R¹ R² R³ R⁴ R⁵ Z R R⁶ 3499 H H i-Pr H MeO Ph3-Me-4-nPrNHCOCH₂O—Ph H 3500 H H i-Pr H HO Ph 3-Cl-4-nPrNHCOCH₂O—Ph H3501 H H i-Pr H Me Ph 4-nPrNHCOCH₂O—Ph H 3502 H H i-Pr H MeO Ph4-MeOCOCH₂NHCOCH₂O—Ph H 3503 H H i-Pr H MeO Ph 4-PhCONHCH₂NHCOCH₂O—Ph Me3504 H H i-Pr H MeO Ph 4-PhCOCH₂NHCOCH₂O—Ph H 3505 H H i-Pr H HOCH₂CH₂Ph 4-nPrNHCOCH₂O—Ph H 3506 H H i-Pr H MeO₂CCH₂ Ph 4-nPrNHCOCH₂O—Ph H3507 H H 2-Pyridyl-PhCH₂ H H Ph 4-nPrNHCOCH₂O—Ph H 3508 H HMeNHCOCH₂O—PhCH₂ H H Ph 4-nPrNHCOCH₂—Ph H

[0250] TABLE 35 [I-3d]

Compound No. R¹ R² R³ R⁴ R⁶ Z R R⁷ 3509 H H i-Pr H Me Ph 4-MeO—Ph Me3510 H H i-Pr H Me Ph 4-HO—Ph Me 3511 H H i-Pr H Me Ph 4-nPrNHCOCH₂O—PhMe 3512 H H i-Pr H HO Ph 4-nPrNHCOCH₂O—Ph Me 3513 H H i-Pr H MeCO Ph4-nPrNHCOCH₂O—Ph Me 3514 H H i-Pr H H₂NCO Ph 4-nPrNHCOCH₂O—Ph Me 3515 HH i-Pr H MeCOCH₂ Ph 4-nPrNHCOCH₂O—Ph Me 3516 H H i-Pr H MeO₂CCH₂ Ph4-nPrNHCOCH₂O—Ph Me 3517 H H i-Pr H Me Ph 4-nPrNHCOCH₂O—Ph Et 3518 H Hi-Pr H Me Ph 4-nPrNHCOCH₂O—Ph Pr 3519 H H 4-MeO—Ph H Me Ph4-nPrNHCOCH₂O—Ph Me 3520 H H (2-pyridyl)CH₂NHCO—Ph H Me Ph4-nPrNHCOCH₂O—Ph Me 3521 H H (3,4-methylenedioxyPh)—Ph H Me Ph4-nPrNHCOCH₂O—Ph Me

[0251] TABLE 36 [I-4]

Com- pound No. R¹ R² R³ R⁴ Z R 4001 H H i-Pr H Ph 2-MeO—Ph 4002 H H i-PrH Ph Ph 4003 H H i-Pr H Ph 2-NH₂—Ph 4004 H H i-Pr H Ph 4-F—Ph 4005 H Hi-Pr H Ph 4-Et₂N—Ph 4006 H H i-Pr H Ph 4-Cl—Ph 4007 H H i-Pr H Ph4-HO—Ph 4008 H H i-Pr H Ph 3-MeO—Ph 4009 H H i-Pr H Ph 3-HO—Ph 4010 H Hi-Pr H Ph 3-NH₂—Ph 4011 H H i-Pr H Ph 4-MeO—Ph 4012 H H i-Pr H Ph4-Me—Ph 4013 H H i-Pr H Ph 3-Me—Ph 4014 H H i-Pr H Ph 4-tBuO₂CCH₂O—Ph4015 H H i-Pr H Ph 4-HO₂CCH₂O—Ph 4016 H H i-Pr H Ph 4-tBuO₂C(CH₂)₅O—Ph4017 H H i-Pr H Ph 4-HO₂C(CH₂)₅O—Ph 4018 H H i-Pr H Ph 4-HO(CH₂)₃O—Ph4019 H H i-Pr H Ph 4-HO(CH₂)₂O—Ph 4020 H H i-Pr H Ph4-HOC(Me)₂(CH₂)₂O—Ph 4021 H H i-Pr H Ph 4-PhCH₂O—Ph 4022 H H i-Pr H Ph4-MeNHCOCH₂O—Ph 4023 H H i-Pr H Ph 4-EtNHCOCH₂O—Ph 4024 H H i-Pr H Ph4-nPrNHCOCH₂O—Ph 4025 H H i-Pr H Ph 4-nBuNHCOCH₂O—Ph 4026 H H i-Pr H Ph4-CH₂═CHCH₂NHCOCH₂O—Ph 4027 H H i-Pr H Ph 4-Me(CH₂)₉NHCOCH₂O—Ph 4028 H Hi-Pr H Ph 4-N₃(CH₂)₃O—Ph 4029 H H i-Pr H Ph 4-tBuO₂CCH(Me)O—Ph 4030 H Hi-Pr H Ph 4-nPrNHCOCH(Me)O—Ph 4031 H H i-Pr H Ph 4-F₃CSO₃—Ph 4032 H Hi-Pr H Ph 4-tBuO₂CCH═CHPh 4033 H H i-Pr H Ph 4-nPrNHCOCH═CH—Ph 4034 H Hi-Pr H Ph 4-nPrCH(Me)NHCOCH₂O—Ph 4035 H H i-Pr H Ph4-EtCH(Me)NHCOCH₂O—Ph 4036 H H i-Pr H Ph 4-MeOCH₂O—Ph 4037 H H i-Pr H Ph4-EtCOCH₂O—Ph 4038 H H i-Pr H Ph 3-tBuO₂CCH₂O—Ph 4039 H H i-Pr H Ph3-HO₂CCH₂O—Ph 4040 H H i-Pr H Ph 3-nPrNHCOCH₂O—Ph 4041 H H i-Pr H Ph4-H₂NC(Me)₂CH₂O₂CCH₂O—Ph 4042 H H i-Pr H Ph 4-morpholinoCOCH₂O—Ph 4043 HH i-Pr H Ph 4-(4-Cl-Ph)-COCH₂O—Ph 4044 H H i-Pr H Ph 4-PhCOCH₂O—Ph 4045H H i-Pr H Ph 4-(4-pyridyl)-CH₂NHCOCH₂O—Ph 4046 H H i-Pr H Ph4-H₂NCH₂CH₂NHCOCH₂O—Ph

[0252] TABLE 37 [I-4]

Compound No. R¹ R² R³ R⁴ Z R 4047 H H i-Pr H Ph 4-Cl-3-NO₂—Ph 4048 H Hi-Pr H Ph 4-Cl-3-F—Ph 4049 H H i-Pr H Ph 4-Cl-3-Me—Ph 4050 H H i-Pr H Ph3-NH₂-4-Cl—Ph 4051 H H i-Pr H Ph 3-Cl-4-MeO—Ph 4052 H H i-Pr H Ph3-Cl-4-Me—Ph 4053 H H i-Pr H Ph 4-Br-3-Cl—Ph 4054 H H i-Pr H Ph4-Br-2-Cl—Ph 4055 H H i-Pr H Ph 4-F-3-Me—Ph 4056 H H i-Pr H Ph3-F-4-Me—Ph 4057 H H i-Pr H Ph 3-Br-4-HO—Ph 4058 H H i-Pr H Ph3-Br-4-MeO—Ph 4059 H H i-Pr H Ph 3-Br-4-F—Ph 4060 H H i-Pr H Ph3-F-4-PhPh 4061 H H i-Pr H Ph 4-HO-3-I—Ph 4062 H H i-Pr H Ph 5-HO-2-I—Ph4063 H H i-Pr H Ph 3-I-4-MeO—Ph 4064 H H i-Pr H Ph 2-I-5-MeO—Ph 4065 H Hi-Pr H Ph 4-MeO-3-Me—Ph 4066 H H i-Pr H Ph 4-HO(CH₂)₃O-3-I—Ph 4067 H Hi-Pr H Ph 4-HO(CH₂)₂O-3-I—Ph 4068 H H i-Pr H Ph 4-HOC(Me)₂(CH₂)₂O-3-I—Ph4069 H H i-Pr H Ph 4-tBuO₂C(CH₂)₄O-3-I—Ph 4070 H H i-Pr H Ph3-I-4-PhCH₂O—Ph 4071 H H i-Pr H Ph 4-H₂NCOCH₂O-3-I—Ph 4072 H H i-Pr H Ph3-I-4-MeNHCOCH₂O—Ph 4073 H H i-Pr H Ph 4-EtNHCOCH₂O-3-I—Ph 4074 H H i-PrH Ph 3-I-4-nPrNHCOCH₂O—Ph 4075 H H i-Pr H Ph 3-I-4-iPrNHCOCH₂O—Ph 4076 HH i-Pr H Ph 4-nBuNHCOCH₂O-3-I—Ph 4077 H H i-Pr H Ph 4-tBuNHCOCH₂O-3-I—Ph4078 H H i-Pr H Ph 4-iBuNHCOCH₂O—Ph 4079 H H i-Pr H Ph4-tBuO₂CCH₂O-3-I—Ph 4080 H H i-Pr H Ph 3-I-4-PhCH₂NHCOCH₂O—Ph 4081 H Hi-Pr H Ph 3-I-4-(2-tetrahydrofurYI)CH₂NHCOCH₂O—Ph 4082 H H i-Pr H Ph4-cycloPrNHCOCH₂O-3-I—Ph 4083 H H i-Pr H Ph 4-cycloPentylNHCOCH₂O-3-I—Ph4084 H H i-Pr H Ph 4-cycloHexylNHCOCH₂O-3-I—Ph 4085 H H i-Pr H Ph4-cycloPrNHCOCH₂O-3-F—Ph 4086 H H i-Pr H Ph 4-Me(CH₂)₉NHCOCH₂O-3-I—Ph4087 H H i-Pr H Ph 4-HO₂CCH₂O-3-I—Ph 4088 H H i-Pr H Ph4-N₃(CH₂)₃O-3-I—Ph 4089 H H i-Pr H Ph 3-I-4-nPrNHCO(CH₂)₄O—Ph 4090 H Hi-Pr H Ph 4-Et₂NCOCH₂O-3-I—Ph 4091 H H i-Pr H Ph 3-I-4-nPrN(Me)COCH₂O—Ph4092 H H i-Pr H Ph 3-Cl-4-nPrNHCOCH₂O—Ph

[0253] TABLE 38 [I-4]

Compound No. R¹ R² R³ R⁴ Z R 4093 H H i-Pr H Ph 3-Br-4-nPrNHCOCH₂O—Ph4094 H H i-Pr H Ph 3-F-4-nPrNHCOCH₂O—Ph 4095 H H i-Pr H Ph3-Me-4-nPrNHCOCH₂O—Ph 4096 H H i-Pr H Ph 4-EtNHCOCH₂O-3-F—Ph 4097 H Hi-Pr H Ph 3-I-4-iPrNHCOC(Me)₂CH₂O—Ph 4098 H H i-Pr H Ph3-Br-4-CH₂═CHCH₂NHCOCH₂O—Ph 4099 H H i-Pr H Ph 4-iBuNHCOCH₂O-3-F—Ph 4100H H i-Pr H Ph 3-tBuO₂CCH═CH-4-nPrNHCOCH₂O—Ph 4101 H H i-Pr H Ph3-HO₂CCH═CH-4-nPrNHCOCH₂O—Ph 4102 H H i-Pr H Ph3-I-4-MeOCH₂CH₂NHCOCH₂O—Ph 4103 H H i-Pr H Ph 3-F-4-HO—Ph 4104 H H i-PrH Ph 3-F-4-MeO—Ph 4105 H H i-Pr H Ph 3,4-methylenedioxyPh 4106 H H i-PrH Ph 3,4-ethylenedioxyPh 4107 H H i-Pr H Ph 3,4-Cl₂—Ph 4108 H H i-Pr HPh 3,4-Me₂—Ph 4109 H H i-Pr H Ph 3,4-F₂—Ph 4110 H H i-Pr H Ph3,4-(MeO)₂—Ph 4111 H H i-Pr H Ph 3,5-(MeO)₂—Ph 4112 H H i-Pr H Ph3,5-Me₂—Ph 4113 H H i-Pr H Ph 3,5-I₂-4-HO—Ph 4114 H H i-Pr H Ph2,4-I₂-5-HO—Ph 4115 H H i-Pr H Ph 3,5-I₂-4-MeO—Ph 4116 H H i-Pr H Ph2,4-I₂-5-MeO—Ph 4117 H H i-Pr H Ph 2,4,6-Me₃—Ph 4118 H H i-Pr H Ph4-HO(CH₂)₃O-3,5-I₂Ph 4119 H H i-Pr H Ph 3,5-I₂-4-nPrNHCOCH₂O—Ph 4120 H Hi-Pr H Ph 2-thienyl 4121 H H i-Pr H Ph 2-furyl 4122 H H i-Pr H Ph3-pyridyl 4123 H H i-Pr H Ph 2-naphthyl 4124 H H i-Pr H Ph5-F-1-naphthyl 4125 H H i-Pr H Ph dibenzothiophene-2-yl 4126 6-F H i-PrH Ph Ph 4127 7-F H i-Pr H Ph Ph 4128 8-F H i-Pr H Ph Ph 4129 9-F H i-PrH Ph Ph 4130 6-MeO H i-Pr H Ph Ph 4131 9-MeO H i-Pr H Ph Ph 4132 6-OH Hi-Pr H Ph Ph 4133 9-OH H i-Pr H Ph Ph 4134 7-NO₂ H i-Pr H Ph Ph 41358-NO₂ H i-Pr H Ph Ph 4136 9-NO₂ H i-Pr H Ph Ph 4137 6-NHPh H i-Pr H PhPh 4138 7-Me₂N H i-Pr H Ph Ph

[0254] TABLE 39 [I-4]

Com- pound No. R¹ R² R³ R⁴ Z R 4139 7-Me H i-Pr H Ph Ph 4140 8-Me H i-PrH Ph Ph 4141 7-t-Bu H i-Pr H Ph Ph 4142 8-t-Bu H i-Pr H Ph Ph 4143 7-BrH i-Pr H Ph Ph 4144 8-Br H i-Pr H Ph Ph 4145 7-Cl H i-Pr H Ph Ph 41468-Cl H i-Pr H Ph Ph 4147 7-Cl 8-Cl i-Pr H Ph Ph 4148 6-Cl 9-Cl i-Pr H PhPh 4149 6-OH 9-I i-Pr H Ph Ph 4150 H H i-Pr H 1,2-naphthyl Ph 4151 H Hi-Pr H 2,3-naphthyl Ph 4152 H H i-Pr H cyclohexenyl Ph 4153 H HD-Leucine H Ph Ph 4154 H H L-Leucine H Ph Ph 4155 H H D-NorLeucine H PhPh 4156 H H L-NorLeucine H Ph Ph 4157 H H D-AlloLeucine H Ph Ph 4158 H HL-AlloLeucine H Ph Ph 4159 H H D-NorValine H Ph Ph 4160 H H L-NorValineH Ph Ph 4161 H H D-Alanine H Ph Ph 4162 H H L-Alanine H Ph Ph 4163 H HD-Arginine H Ph Ph 4164 H H L-Arginine H Ph Ph 4165 H H D-Asparagine HPh Ph 4166 H H L-Asparagine H Ph Ph 4167 H H D-Glutamic H Ph Ph Acid4168 H H L-Glutamic H Ph Ph Acid 4169 H H D-Glutamine H Ph Ph 4170 H HL-Glutamine H Ph Ph 4171 H H D-Histidine H Ph Ph 4172 H H L-Histidine HPh Ph 4173 H H D-Methionine H Ph Ph 4174 H H L-Methionine H Ph Ph 4175 HH D-Tryptophan H Ph Ph 4176 H H L-Tryptophan H Ph Ph 4177 H H D-TyrosineH Ph Ph 4178 H H L-Tyrosine H Ph Ph 4179 H H D-Homo H Ph PhPhenylalanine 4180 H H L-Homo H Ph Ph Phenylalanine 4181 H H D-Leucine HPh 4-Cl—Ph 4182 H H L-Leucine H Ph 4-Cl—Ph 4183 H H D-NorLeucine H Ph4-Cl—Ph

[0255] TABLE 40 [I-4]

Compound No. R¹ R² R³ R⁴ Z R 4184 H H L-NorLeucine H Ph 4-Cl—Ph 4185 H HD-AlloLeucine H Ph 4-Cl—Ph 4186 H H L-AlloLeucine H Ph 4-Cl—Ph 4187 H HD-NorValine H Ph 4-Cl—Ph 4188 H H L-NorValine H Ph 4-Cl—Ph 4189 H HD-Alanine H Ph 4-Cl—Ph 4190 H H L-Alanine H Ph 4-Cl—Ph 4191 H HD-Arginine H Ph 4-Cl—Ph 4192 H H L-Arginine H Ph 4-Cl—Ph 4193 H HD-Asparagine H Ph 4-Cl—Ph 4194 H H L-Asparagine H Ph 4-Cl—Ph 4195 H HD-Glutamic Acid H Ph 4-Cl—Ph 4196 H H L-Glutamic Acid H Ph 4-Cl—Ph 4197H H D-Glutamine H Ph 4-Cl—Ph 4198 H H L-Glutamine H Ph 4-Cl—Ph 4199 H HD-Histidine H Ph 4-Cl—Ph 4200 H H L-Histidine H Ph 4-Cl—Ph 4201 H HD-Methionine H Ph 4-Cl—Ph 4202 H H L-Methionine H Ph 4-Cl—Ph 4203 H HD-Tryptophan H Ph 4-Cl—Ph 4204 H H L-Tryptophan H Ph 4-Cl—Ph 4205 H HD-Tyrosine H Ph 4-Cl—Ph 4206 H H L-Tyrosine H Ph 4-Cl—Ph 4207 H H D-HomoPhenylalanine H Ph 4-Cl—Ph 4208 H H L-Homo Phenylalanine H Ph 4-Cl—Ph4209 H H t-Bu H Ph Ph 4210 H H (CH₃)₂(OH)C H Ph Ph 4211 H H CH₃(MeO)CH HPh Ph 4212 H H 4-HO—Ph H Ph Ph 4213 H H 4-HO-3-I—Ph H Ph Ph 4214 H H4-HO-3,5-I₂—Ph H Ph Ph 4215 H H 4-HO-3-I—PhCH₂ H Ph Ph 4216 H H4-HO-3,5-I₂—PhCH₂ H Ph Ph 4217 H H 1-naphthylmethyl H Ph Ph 4218 H H4-F—PhCH₂ H Ph Ph 4219 H H 1-naphthylmethyl H Ph 4-Cl—Ph 4220 H H4-F—PhCH₂ H Ph 4-Cl—Ph 4221 H H i-Pr Me Ph 4-Cl—Ph 4222 H H Me Me Ph Ph4223 H H (Combined with R⁴) CH₂ — Ph Ph 4224 H H (Combined with R⁴) MeCH— Ph Ph 4225 H H (Combined with R⁴) (CH₂)₄ — Ph Ph 4226 H H i-Pr H Ph4-n-PrNHCOCH₂CH₂O—Ph 4227 H H i-Pr H Ph 4-i-PrNHCOCH₂CH₂O—Ph 4228 H Hi-Pr H Ph 4-EtNHCOCH₂CH₂O—Ph

[0256] TABLE 41 [I-4]

Compound No. R¹ R² R³ R⁴ Z R 4229 H H i-Pr H Ph 4-EtCH(Me)NHCOCH₂CH₂O-Ph4230 H H i-Pr H Ph 3-Cl-4-i-PrNHCOCH₂O-Ph 4231 H H i-Pr H Ph3-Cl-4-EtNHCOCH₂O-Ph 4232 H H i-Pr H Ph 3-Cl-4-EtCH(Me)NHCOCH₂O-Ph 4233H H i-Pr H Ph 4-i-PrNHCOCH₂O-3-Me-Ph 4234 H H i-Pr H Ph4-EtNHCOCH₂O-3-Me-Ph 4235 H H i-Pr H Ph 4-EtCH(Me)NHCOCH₂O-3-Me-Ph 4236H H i-Pr H Ph 4-cycloPrNHCOCH₂CH₂O-Ph 4237 H H i-Pr H Ph4-cycloPentylNHCOCH₂CH₂O-Ph 4238 H H i-Pr H Ph 3-I-4-n-PrNHCOCH₂CH₂O-Ph4239 H H i-Pr H Ph 3-I-4-i-PrNHCOCH₂CH₂O-Ph 4240 H H i-Pr H Ph4-EtNHCOCH₂CH₂O-3-I-Ph 4241 H H i-Pr H Ph 4-EtCH(Me)NHCOCH₂CH₂O-3-I-Ph4242 H H i-Pr H Ph 4-EtCOCH₂CH₂O-3-I-Ph 4243 H H i-Pr H Ph4-cycloPrNHCOCH₂CH₂O-3-I-Ph 4244 H H i-Pr H Ph4-cycloPentylNHCOCH₂CH₂O-3-I-Ph 4245 H H i-Pr H Ph3-F-4-n-PrNHCOCH₂CH₂O-Ph 4246 H H i-Pr H Ph 3-F-4-i-PrNHCOCH₂CH₂O-Ph4247 H H i-Pr H Ph 4-EtNHCOCH₂CH₂O-3-F-Ph 4248 H H i-Pr H Ph4-EtCH(Me)NHCOCH₂CH₂O-3-F-Ph 4249 H H i-Pr H Ph 4-EtCOCH₂CH₂O-3-F-Ph4250 H H i-Pr H Ph 3-F-4-i-BuNHCOOH₂CH₂O-Ph 4251 H H i-Pr H Ph4-cycloPrNHCOCH₂CH₂O-3-F-Ph 4252 H H i-Pr H Ph 3-Br-4-n-PrNHCOCH₂CH₂O-Ph4253 H H i-Pr H Ph 3-Br-4-i-PrNHCOCH₂CH₂O-Ph 4254 H H i-Pr H Ph3-Br-4-EtNHCOCH₂CH₂O-Ph 4255 H H i-Pr H Ph 3-Br-4-i-BuNHCOCH₂CH₂O-Ph4256 H H i-Pr H Ph 3-Cl-4-n-PrNHCOCH₂CH₂O-Ph 4257 H H i-Pr H Ph3-Cl-4-i-PrNHCOCH₂CH₂O-Ph 4258 H H i-Pr H Ph 3-Cl-4-EtNHCOCH₂CH₂O-Ph4259 H H i-Pr H Ph 3-Cl-4-EtCH(Me)NHCOCH₂CH₂O-Ph 4260 H H i-Pr H Ph3-Cl-4-cycloPrNHCOCH₂CH₂O-Ph 4261 H H i-Pr H Ph3-Cl-4-cycloPentylNHCOCH₂CH₂O-Ph 4262 H H i-Pr H Ph3-Me-4-n-PrNHCOCH₂CH₂O-Ph 4263 H H i-Pr H Ph 4-i-PrNHCOCH₂CH₂O-3-Me-Ph4264 H H i-Pr H Ph 4-EtNHCOCH₂CH₂O-3-Me-Ph 4265 H H i-Pr H Ph3-Me-4-MeNHCOCH₂CH₂O-Ph 4266 H H i-Pr H Ph 3-Me-4-n-BuNHCOCH₂CH₂O-Ph4267 H H i-Pr H Ph 4-EtCH(Me)NHCOCH₂CH₂O-3-Me-Ph 4268 H H i-Pr H Ph4-EtCOCH₂CH₂O-3-Me-Ph 4269 H H i-Pr H Ph 4-i-BuNHCOCH₂CH₂O-3-Me-Ph 4270H H i-Pr H Ph 3-Me-4-t-BuNHCOCH₂CH₂O-Ph 4271 H H i-Pr H Ph4-cycloPrNHCOCH₂CH₂O-3-Me-Ph 4272 H H i-Pr H Ph4-cycloPentylNHCOCH₂CH₂O-3-MePh 4273 H H Me H Ph 3-Cl-4-n-PrNHCOCH₂O-Ph

[0257] TABLE 42 [I-4]

Compound No. R¹ R² R³ R⁴ Z R 4274 H H Me H Ph 3-Cl-4-i-PrNHCOCH₂O-Ph4275 H H Me H Ph 3-Cl-4-EtNHCOCH₂O-Ph 4276 H H Me H Ph3-Cl-4-EtCH(Me)NHCOCH₂O-Ph 4277 H H Me H Ph 3-Cl-4-cycloPrNHCOCH₂O-Ph4278 H H Me H Ph 3-Cl-4-cycloPentylNHCOCH₂O-Ph 4279 H H Et H Ph3-Me-4-n-PrNHCOCH₂O-Ph 4280 H H Et H Ph 4-i-PrNHCOCH₂O-3-Me-Ph 4281 H HEt H Ph 4-EtNHCOCH₂O-3-Me-Ph 4282 H H Et H Ph 3-Me-4-MeNHCOCH₂O-Ph 4283H H Et H Ph 3-Me-4-n-BuNHCOCH₂O-Ph 4284 H H Et H Ph4-EtCH(Me)NHCOCH₂O-3-Me-Ph 4285 H H Et H Ph 4-EtCOCH₂O-3-Me-Ph 4286 H HEt H Ph 4-i-BuNHCOCH₂O-3-Me-Ph 4287 H H Pr H Ph 3-Cl-4-n-PrNHCOCH₂O-Ph4288 H H Pr H Ph 3-Cl-4-i-PrNHCOCH₂O-Ph 4289 H H Pr H Ph3-Cl-4-EtNHCOCH₂O-Ph 4290 H H Pr H Ph 3-Cl-4-EtCH(Me)NHCOCH₂O-Ph 4291 HH Pr H Ph 3-Cl-4-cycloPrNHCOCH₂O-Ph 4292 H H Pr H Ph3-Cl-4-cycloPentylNHCOCH₂O-Ph 4293 H H Bu H Ph 3-Me-4-n-PrNHCOCH₂O-Ph4294 H H Bu H Ph 4-i-PrNHCOCH₂O-3-Me-Ph 4295 H H Bu H Ph4-EtNHCOCH₂O-3-Me-Ph 4296 H H Bu H Ph 3-Me-4-MeNHCOCH₂O-Ph 4297 H H Bu HPh 3-Me-4-n-BuNHCOCH₂O-Ph 4298 H H Bu H Ph 4-EtCH(Me)NHCOCH₂O-3-Me-Ph4299 H H Bu H Ph 4-EtCOCH₂O-3-Me-Ph 4300 H H Bu H Ph4-i-BuNHCOCH₂O-3-Me-Ph 4301 H H i-Bu H Ph 3-Cl-4-nPrNHCOCH₂O-Ph 4302 H Hi-Bu H Ph 3-Cl-4-i-PrNHCOCH₂O-Ph 4303 H H i-Bu H Ph 3-Cl-4-EtNHCOCH₂O-Ph4304 H H i-Bu H Ph 3-Cl-4-EtOH(Me)NHCOCH₂O-Ph 4305 H H i-Bu H Ph3-Cl-4-cycloPrNHCOCH₂O-Ph 4306 H H i-Bu H Ph3-Cl-4-cycloPentylNHCOCH₂O-Ph 4307 H H t-Bu H Ph 3-Me-4-n-PrNHCOCH₂O-Ph4308 H H t-Bu H Ph 4-i-PrNHCOCH₂O-3-Me-Ph 4309 H H t-Bu H Ph4-EtNHCOCH₂O-3-Me-Ph 4310 H H t-Bu H Ph 3-Me-4-MeNHCOCH₂O-Ph 4311 H HPhCH₂ H Ph 3-Me-4-n-BuNHCOCH₂O-Ph 4312 H H PhCH₂ H Ph4-EtOH(Me)NHCOCH₂O-3-Me-Ph 4313 H H PhCH₂ H Ph 4-EtCOCH₂O-3-Me-Ph 4314 HH PhCH₂ H Ph 4-i-BuNHCOCH₂O-3-Me-Ph 4315 H H i-Pr Me Ph3-Cl-4-n-PrNHCOCH₂O-Ph 4316 H H i-Pr Me Ph 3-Cl-4-i-PrNHCOCH₂O-Ph 4317 HH i-Pr Me Ph 3-Cl-4-EtNHCOCH₂O-Ph 4318 H H i-Pr Me Ph3-Cl-4-EtCH(Me)NHCOCH₂O-Ph

[0258] TABLE 43 [I-4]

Compound No. R¹ R² R³ R⁴ Z R 4319 H H i-Pr Me Ph3-Cl-4-cycloPrNHCOCH₂O-Ph 4320 H H i-Pr Me Ph3-Cl-4-cycloPentylNHCOCH₂O-Ph 4321 H H i-Pr H 2,3-Pyridyl3-Me-4-n-PrNHCOCH₂O-Ph 4322 H H i-Pr H 2,3-Pyridyl4-i-PrNHCOCH₂O-3-Me-Ph 4323 H H i-Pr H 2,3-Pyridyl 4-EtNHCOCH₂O-3-Me-Ph4324 H H i-Pr H 2,3-Pyridyl 3-Me-4-MeNHCOCH₂O-Ph 4325 H H i-Pr H2,3-Pyridyl 3-Me-4-n-BuNHCOCH₂O-Ph 4326 H H i-Pr H 2,3-Pyridyl4-EtCH(Me)NHCOCH₂O-3-Me-Ph 4327 H H i-Pr H 2,3-Pyridyl4-EtCOCH₂O-3-Me-Ph 4328 H H i-Pr H 2,3-Pyridyl 4-i-BuNHCOCH₂O-3-Me-Ph4329 H H i-Pr H 2,3-Pyridyl 3-Cl-4-n-PrNHCOCH₂O-Ph 4330 H H i-Pr H3,4-Pyridyl 3-Cl-4-i-PrNHCOCH₂O-Ph 4331 H H i-Pr H 3,4-Pyridyl3-Cl-4-EtNHCOCH₂O-Ph 4332 H H i-Pr H 3,4-Pyridyl3-Cl-4-EtCH(Me)NHCOCH₂O-Ph 4333 H H i-Pr H 3,4-Pyridyl3-Cl-4-cycloPrNHCOCH₂O-Ph 4334 H H i-Pr H 3,4-Pyridyl3-Cl-4-cycloPentylNHCOCH₂O-Ph 4335 H H i-Pr H Ph4-F-5-n-PrNHCOCH₂O-(2-pyridyl) 4336 H H i-Pr H Ph4-F-5-i-PrNHCOCH₂₂O-(2-pyridyl) 4337 H H i-Pr H Ph4-EtNHCOCH₂O-3-F-(2-pyridyl) 4338 H H i-Pr H Ph4-EtCH(Me)NHCOCH₂O-3-F-(2-pyridyl) 4339 H H i-Pr H Ph4-EtCOCH₂O-3-F-(2-pyridyl) 4340 H H i-Pr H Ph3-F-4-i-BuNHCOCH₂O-(2-pyridyl) 4341 H H i-Pr H Ph4-cycloPrNHCOCH₂O-3-F-(2-pyridyl) 4342 H H i-Pr H Ph5-I-6-n-PrNHCOCH₂O-(3-pyridyl) 4343 H H i-Pr H Ph5-I-6-i-PrNHCOCH₂O-(3-pyridyl) 4344 H H i-Pr H Ph6-EtNHCOCH₂O-5-I-(3-pyridyl) 4345 H H i-Pr H Ph6-EtCH(Me)NHCOCH₂O-5-I-(3-pyridyl) 4346 H H i-Pr H Ph6-EtCOCH₂O-5-I-(3-pyridyl) 4347 H H i-Pr H Ph6-cycloPrNHCOCH₂O-5-I-(3-pyridyl) 4348 H H i-Pr H Ph3-NO₂-4-n-PrNHCOCH₂O-Ph 4349 H H i-Pr H Ph 3-NO₂-4-i-PrNHCOCH₂O-Ph 4350H H i-Pr H Ph 4-EtNHCOCH₂O-3-NO₂-Ph 4351 H H i-Pr H Ph4-EtCH(Me)NHCOCH₂O-3-NO₂-Ph 4352 H H i-Pr H Ph 4-EtCOCH₂O-3-NO₂-Ph 4353H H i-Pr H Ph 4-i-BuNHCOCH₂O-3-NO₂-Ph 4354 H H i-Pr H Ph4-cycloPrNHCOCH₂O-3-NO₂-Ph 4355 H H i-Pr H Ph 3-MeO-4-n-PrNHCOCH₂O-Ph4356 H H i-Pr H Ph 3-MeO-4-i-PrNHCOCH₂O-Ph 4357 H H i-Pr H Ph4-EtNHCOCH₂O-3-MeO-Ph 4358 H H i-Pr H Ph 4-EtCH(Me)NHCOCH₂O-3-MeO-Ph4359 H H i-Pr H Ph 4-EtCOCH₂O-3-MeO-Ph 4360 H H i-Pr H Ph3-MeO-4-i-BuNHCOCH₂O-Ph 4361 H H i-Pr H Ph 4-cycloPrNHCOCH₂O-3-MeO-Ph4362 H H i-Pr H Ph 3-HO-4-n-PrNHCOCH₂O-Ph 4363 H H i-Pr H Ph3-HO-4-i-PrNHCOCH₂O-Ph

[0259] TABLE 44 [I-4]

Compound No. R¹ R² R³ R⁴ Z R 4364 H H i-Pr H Ph 4-EtNHCOCH₂O-3-HO-Ph4365 H H i-Pr H Ph 4-EtCH(Me)NHCOCH₂O-3-HO-Ph 4366 H H i-Pr H Ph4-EtCOCH₂O-3-HO-Ph 4367 H H i-Pr H Ph 3-HO-4-i-BuNHCOCH₂O-Ph 4368 H Hi-Pr H Ph 4-cycloPrNHCOCH₂O-3-HO-Ph 4369 H H i-Pr H Ph3-H₂NCH₂CH₂NHCOCH₂O-Ph 4370 H H i-Pr H Ph 2-H₂NCH₂CH₂NHCOCH₂O-Ph 4371 HH i-Pr H Ph 4-MeNHCH₂CH₂NHCOCH₂O-Ph 4372 H H i-Pr H Ph3-MeNHCH₂CH₂NHCOCH₂O-Ph 4373 H H i-Pr H Ph 2-MeNHCH₂CH₂NHCOCH₂O-Ph 4374H H i-Pr H Ph 4-Me₂NCH₂CH₂NHCOCH₂O-Ph 4375 H H i-Pr H Ph3-Me₂NCH₂CH₂NHCOCH₂O-Ph 4376 H H i-Pr H Ph 2-Me₂NCH₂CH₂NHCOCH₂O-Ph 4377H H i-Pr H Ph 4-H₂NCH₂CH₂NHCOCH₂O-3-Cl-Ph 4378 H H i-Pr H Ph3-H₂NCH₂CH₂NHCOCH₂O-4-Cl-Ph 4379 H H i-Pr H Ph2-H₂NCH₂CH₂NHCOCH₂O-4-Cl-Ph 4380 H H i-Pr H Ph4-MeNHCH₂CH₂NHCOCH₂O-3-Me-Ph 4381 H H i-Pr H Ph3-MeNHCH₂CH₂NHCOCH₂O-4-Me-Ph 4382 H H i-Pr H Ph2-MeNHCH₂CH₂NHCOCH₂O-4-MePh 4383 H H i-Pr H Ph4-Me₂NCH₂CH₂NHCOCH₂O-3-F-Ph 4384 H H i-Pr H Ph3-Me₂NCH₂CH₂NHCOCH₂O-4-F-Ph 4385 H H i-Pr H Ph2-Me₂NCH₂CH₂NHCOCH₂O-4-F-Ph 4386 H H i-Pr H Ph 4-H₂NCOCH₂-3-I-Ph 4387 HH i-Pr H Ph 3-I-4-MeNHCOCH₂-Ph 4388 H H i-Pr H Ph 4-EtNHCOCH₂-3-I-Ph4389 H H i-Pr H Ph 3-I-4-nPrNHCOCH₂-Ph 4390 H H i-Pr H Ph3-I-4-iPrNHCOCH₂-Ph 4391 H H i-Pr H Ph 4-nBuNHCOCH₂-3-I-Ph 4392 H H i-PrH Ph 4-tBuNHCOCH₂-3-I-Ph 4393 H H i-Pr H Ph 4-iBuNHCOCH₂-Ph 4394 H Hi-Pr H Ph 4-tBuO₂CCH₂-3-I-Ph 4395 H H i-Pr H Ph 3-I-4-PhCH₂NHCOCH₂-Ph4396 H H i-Pr H Ph 3-I-4-(2-tetrahydrofuryl)CH₂NHCOCH₂-Ph 4397 H H i-PrH Ph 4-cycloPrNHCOCH₂-3-I-Ph 4398 H H i-Pr H Ph4-cycloPentylNHCOCH₂-3-I-Ph 4399 H H i-Pr H Ph4-cycloHexylNHCOCH₂-3-I-Ph 4400 H H i-Pr H Ph 4-cycloPrNHCOCH₂-3-F-Ph4401 H H i-Pr H Ph 3-Cl-4-i-PrNHCOCH₂CH₂-Ph 4402 H H i-Pr H Ph3-Cl-4-EtNHCOCH₂CH₂-Ph 4403 H H i-Pr H Ph 3-Cl-4-EtCH(Me)NHCOOH₂CH₂-Ph4404 H H i-Pr H Ph 4-i-PrNHCO-3-Me-Ph 4405 H H i-Pr H Ph4-EtNHCO-3-Me-Ph 4406 H H i-Pr H Ph 4-EtCH(Me)NHCO-3-Me-Ph 4407 H H i-PrH Ph 3-Cl-4-i-PrNHCH₂CH₂O-Ph 4408 H H i-Pr H Ph 3-Cl-4-EtNHCH₂CH₂O-Ph4409 H H i-Pr H Ph 3-Cl-4-EtCH(Me)NHCH₂CH₂O-Ph

[0260] TABLE 45 [I-4]

Compound No. R¹ R² R³ R⁴ Z R 4410 H H i-Pr H 4,5-pyridazinyl4-nPrNHCOCH₂O-Ph 4411 H H i-Pr H 5,6-benztrizolyl 4-nPrNHCOCH₂O-Ph 4412H H i-Pr H 1,2-cyclohexyl 4-nPrNHCOCH₂O-Ph 4413 H H i-Pr H6,7-phthalazinyl 4-nPrNHCOCH₂O-Ph 4414 H H i-Pr H 6,7-quinoxatinyl4-nPrNHCOCH₂O-Ph 4415 H H i-Pr H Ph 3-PhSO₂-4-nPrNHCOCH₂O-Ph 4416 H Hi-Pr H Ph 3-EtNH₂-4-nPrNHCOCH₂O-Ph 4417 H H i-Pr H Ph3-Me-4-nPrNHCOCH₂S-Ph 4418 H H i-Pr H Ph 3-Me-4-Et₂NCOCH₂S-Ph 4419 H Hi-Pr H Ph 4-nPrNHCOCH₂O-pyrazin-2-yl 4420 H H i-Pr H Ph3-(2,5-Pyrazinyl)-4-n-PrNHCOCH₂O-Ph 4421 H H i-Pr H Ph3-(3,4-methylenedioxyPh)-4-EtNHCOCH₂O-Ph 4422 H H i-Pr H Ph3-Me-4-nPrNHCOCH₂NH-Ph 4423 H H i-Pr H Ph 3-Me-4-nPrNHCOCH₂S-Ph 4424 H Hi-Pr H Ph 3-Cl-4-HO-Ph 4425 H H n-PrNHCS-PhCH₂ H Ph 4-nPrNHCOCH₂O-Ph4426 H H (3-thienyl)CH₂ H Ph 4-nPrNHCOCH₂O-Ph 4427 H H3,4-ethytenedioxyPhCH₂ H Ph 4-nPrNHCOCH₂O-Ph

[0261] Among these compounds, preferred ones are, for example, compoundsof 1002, 1011, 1014, 1023, 1024, 1033, 1035, 1037, 1046, 1050, 1056,1063, 1070, 1071, 1072, 1073, 1074, 1075, 1076, 1077, 1078, 1081, 1082,1083, 1085, 1091, 1092, 1093, 1094, 1095, 1096, 1098, 1102, 1104, 1107,1119, 1122, 1126, 1129, 1130, 1137, 1150, 1152, 1182, 1183, 1184, 1185,1209, 1210, 1219, 1251, 1257, 1268, 1276, 1285, 1295, 1310, 1316, 1413,1426, 1429, 1430, 1432, 1433, 1435, 1328, 1333, 1338, 1348, 1356, 1364,1371, 1380, 1383, 1388, 1391, 1404, 2002, 2011, 2023, 2024, 2050, 2056,2074, 2092, 2094, 2096, 2251, 2268, 2285, 2295, 2316, 2333, 2348, 2364,2380, 2388, 2391, 2410, 2422, 2456, 2462, 2467, 2468, 2471, 2474, 2476,3001, 3002, 3007, 3011, 3014, 3015, 3020, 3023, 3024, 3033, 3039, 3047,3050, 3051, 3056, 3057, 3058, 3063, 3065, 3072, 3073, 3074, 3076, 3078,3082, 3083, 3092, 3093, 3094, 3095, 3096, 3103, 3104, 3107, 3117, 3226,3241, 3246, 3258, 3266, 3296, 3307, 3319, 3412, 3418, 3464, 3468, 3471,3475, 3476, 3477, 3479, 3480, 3481, 3482, 3484, 3485, 3486, 3487, 3488,3489, 3492, 3493, 3495, 3499, 3500, 3501, 3505, 3506, 3509, 3510, 3511,3513, 3515, 3516, 3517, 3518, 4002, 4011, 4023, 4024, 4050, 4056, 4063,4073, 4074, 4092, 4094, 4096, 4257, 4276, 4295, 4316, 4333, 4348, 4364,4380, 4388, 4404, 4410, 4416, 4417, 4419, 4420, etc, and furtherpreferred ones are, for example, compounds of 1002, 1014, 1024, 1033,1050, 1063, 1071, 1072, 1073, 1074, 1075, 1076, 1078, 1081, 1082, 1083,1091, 1092, 1093, 1094, 1095, 1098, 1102, 1104, 1209, 1429, 1430, 1432,1433, 1435, 2002, 2011, 2050, 2074, 2094, 2268, 2295, 2333, 2364, 2380,2391, 2410, 2422, 2456, 2462, 2471, 3001, 3002, 3007, 3011, 3014, 3015,3024, 3050, 3056. 3063, 3074, 3078, 3082, 3092, 3093, 3094, 3095, 3103,3104, 3475, 3476, 3477, 3479, 3480, 3481, 3482, 3488, 3489, 3499, 3511,4002, 4011, 4050, 4063, 4073, 4074, 4094, 4257, 4295, 4333, 4348, 4380,4388, 4404 , etc.

[0262] Particularly preferred compounds among these compounds are asfollows:

[0263]2-(4-(3-isopropyl-2,5-dioxo-2,3-dihydro[1,3]oxazolo[2,3-a]isoindol-9(5H)-yl)phenoxy)-N-propylacetamide(compound of 1024),

[0264]9b-(3-iodo-4-methoxyphenyl)-3-isopropyl[1,3]oxazolo[2,3-a]isoindole-2,5(3H,9bH)-dione(compound of 1063),

[0265]2-(2-iodo-4-(3-isopropyl-2,5-dioxo-2,3-dihydro[1,3]oxazolo[2,3-a]isoindol-9(5H)-yl)phenoxy)-N-methylacetamide(compound of 1072),

[0266]N-ethyl-2-(2-iodo-4-(3-isopropyl-2,5-dioxo-2,3-dihydro[1,3]oxazolo[2,3-a]isoindol-9(5H)-yl)phenoxy)acetamide(compound of 1073),

[0267]2-(2-iodo-4-(3-isopropyl-2,5-dioxo-2,3-dihydro[1,3]oxazolo[2,3-a]isoindol-9(5H)-yl)phenoxy)-N-propylacetamide(compound of 1074),

[0268]2-(2-chloro-4-(3-isopropyl-2,5-dioxo-2,3-dihydro[1,3]oxazolo[2,3-a]isoindol-9(5H)-yl)phenoxy)-N-propylacetamide(compound of 1092),

[0269]2-(2-bromo-4-(3-isopropyl-2,5-dioxo-2,3-dihydro[1,3]oxazolo[2,3-a]isoindol-9(5H)-yl)phenoxy)-N-propylacetamide(compound of 1093),

[0270]2-(2-fluoro-4-(3-isopropyl-2,5-dioxo-2,3-dihydro[1,3]oxazolo[2,3-a]isoindol-9(5H)-yl)phenoxy)-N-propylacetamide(compound of 1094),

[0271]2-(4-(3-isopropyl-2,5-dioxo-2,3-dihydro[1,3]oxazolo[2,3-a]isoindol-9(5H)-yl)-2-methylphenoxy)-N-propylacetamide(compound of 1095),

[0272] 2-(2-ethyl-4-(3-isopropyl-2,5-dioxo-2,3-dihydro[1,3]oxazolo[2,3-a]isoindol-9(5H)-yl)phenoxy)-N-propylacetamide(compound of 1435),

[0273]2-(2-iodo-4-(3-isopropyl-2,5-dioxo-2,3-dihydro-1H-imidazo[2,1-a]isoindol-9(5H)-yl)phenoxy)-N-propylacetamide(compound of 2074),

[0274]2-(4-(3-isopropyl-1-methyl-2,5-dioxo-2,3-dihydro-1H-imidazo[2,1-a]isoindol-9(5H)-yl)phenoxy)-N-propylacetamide(compound of 2471),

[0275] 3-isopropyl-9b-(4-methoxyphenyl)-1H-pyrrolo[2,1-a]isoindole-2,5(3H,9bH)-dione (compound of 3011),

[0276]2-(4-(3-isopropyl-2,5-dioxo-2,3-dihydro-1H-pyrrolo[2,1-a]isoindol-9(5H)-yl)phenoxy)-N-propylacetamide(compound of 3024),

[0277]9b-(3-fluoro-4-methylphenyl)-3-isopropyl-1H-pyrrolo[2,1-a]isoindole-2,5(3H,9bH)-dione(compound of 3056),

[0278]2-(2-iodo-4-(3-isopropyl-2,5-dioxo-2,3-dihydro-1H-pyrrolo[2,1-a]isoindol-9(5H)-yl)phenoxy)-N-propylacetamide(compound of 3074),

[0279]2-(2-chloro-4-(3-isopropyl-2,5-dioxo-2,3-dihydro-1H-pyrrolo[2,1-a]isoindol-9(5H)-yl)phenoxy-N-propylacetamide(compound of 3092),

[0280]2-(2-bromo-4-(3-isopropyl-2,5-dioxo-2,3-dihydro-1H-pyrrolo[2,1-a]isoindol-9(5H)-yl)phenoxy)-N-propylacetamide(compound of 3093),

[0281]2-(2-fluoro-4-(3-isopropyl-2,5-dioxo-2,3-dihydro-1H-pyrrolo[2,1-a]isoindol-9(5H)-yl)phenoxy)-N-propylacetamide(compound of 3094),

[0282]2-(4-(3-isopropyl-2,5-dioxo-2,3-dihydro-1H-pyrrolo[2,1-a]isoindol-9(5H)-yl)-2-methylphenoxy)-N-propylacetamide(compound of 3095),

[0283]2-(4-(3-isopropyl-2,5-dioxo-2,3-dihydro-1H-pyrrolo[2,1-a]isoindol-9(5H)-yl)-2-methylphenoxy)-N-propylethanethioamide(compound of 3476),

[0284]2-(2,6-dichloro-4-(3-isopropyl-2,5-dioxo-2,3-dihydro-1H-pyrrolo[2,1-a]isoindol-9(5H)-yl)phenoxy)-N-propylethanethioamide(compound of 3477),

[0285]2-(4-(3-isopropyl-1-methyl-2,5-dioxo-2,3-dihydro-1H-pyrrolo[2,1-a]isoindol-9(5H)-yl)phenoxy)-N-propylacetamide(compound of 3481),

[0286]2-(2,6-dichloro-4-(3-isopropyl-2-oxo-5-thioxo-2,3-dihydro-1H-pyrrolo[2,1-a]isoindol-9(5H)-yl)phenoxy)-N-propylethanethioamide(compound of 3489),

[0287]2-(4-(3-isopropyl-2-(methoxyimino)-5-oxo-1H-pyrrolo[2,1-a]isoindol-9(3H,5H)-yl)-2-methylphenoxy)-N-propylacetamide(compound of 3499),

[0288]2-(4-(3-isopropyl-1,1-dimethyl-2,5-dioxo-2,3-dihydro-1H-pyrrolo[2,1-a]isoindol-9(5H)-yl)phenoxy)-N-propylacetamide(compound of 3511),

[0289]9b-(3-iodo-4-methoxyphenyl)-3-isopropyl[1,3]thiazolo[2,3-a]isoindole-2,5(3H,9bH)-dione(compound of 4063),

[0290]N-ethyl-2-(2-iodo-4-(3-isopropyl-2,5-dioxo-2,3-dihydro[1,3]thiazolo[2,3-a]isoindol-9(5H)-yl)phenoxy)acetamide(compound of 4073),

[0291]2-(2-iodo-4-(3-isopropyl-2,5-dioxo-2,3-dihydro[1,3]thiazolo[2,3-a]isoindol-9(5H)-yl)phenoxy)-N-propylacetamide(compound of 4074), etc.

[0292] Next, description is made on processes for preparing compounds ofthe general formula [I] of the invention.

[0293] Preparation Process A

[0294] This preparation process is for preparation of the compounds ofthe general formula [I-1], the compounds of the general formula [I-2] orthe compounds of the general formula [I-3] of the invention, wherein Yis an oxygen atom, a group NR⁵ or a group CR⁶R⁷ (wherein R⁵, R⁶ and R⁷are as defined above) in the compounds of the general formula [I]. Thecompounds of the general formula [I-1] or the compounds of the generalformula [I-2] of the invention can not only be synthesized in a usualliquid phase, but also using a solid phase, for example using thecombinatorial synthetic method or the parallel synthetic method,remarkably developing in the recent years.

[0295] (First Step)

[0296] A carboxylic acid or thiocarboxylic acid represented by thegeneral formula [II]

[0297] [wherein,

[0298] R⁰ represents (1) an aryl group; (2) a mono- to tricyclic C₇-C₁₅aromatic carbocyclic group selected from the group consisting ofacenaphthylenyl, adamantyl, anthryl, indenyl, norbornyl and phenanthryl;(3) a 5- or 6-membered heterocyclic group selected from the groupconsisting of the aforementioned series of groups A; or (4) a monocyclicto tricyclic aromatic heterocyclic groups having per one ring 1 to 5hetero atoms selected from the group consisting of nitrogen atoms,oxygen atoms and sulfur atoms, selected from the group consisting of theaforementioned series of groups B,

[0299] each of which groups (1) to (4) may optionally have one or moresubstituents selected from the group consisting of the aforementionedseries of groups C provided that amino, carboxyl, hydroxyl, N-aminoC₁-C₁₀ alkylcarbamoyl and amino C₁-C₆ alkoxycarbonyl may optionally beprotected,

[0300] R¹⁰ and R²⁰ are the same or different, and represent groupsselected from the group consisting of the aforementioned series ofgroups D provided that amino, carboxyl and hydroxyl may optionally beprotected; or straight-chain saturated C₁-C₉ aliphatic groups,straight-chain unsaturated C₁-C₉ aliphatic groups, branched saturatedC₁-C₉ aliphatic groups or branched unsaturated C₁-C₉ aliphatic groups,N—C₁-C₆ alkylamino groups, C₁-C₆ alkylthio groups or C₁-C₆ alkoxygroups, each of which groups may optionally be substituted with theabove-mentioned group, and

[0301] X₂ and Z are as defined above]is reacted with an amine compoundsrepresented by the general formula [III]

[0302] [wherein,

[0303] Y₁₀ represents an oxygen atom, a group NR⁵⁰ or a group CR⁶⁰R⁷,and herein,

[0304] R⁵⁰ represents a group selected from the group consisting ofhydrogen, a protective group for amino groups, halogen, optionallyprotected hydroxyl, N—C₁-C₆ alkylsulfonylamino, C₁-C₆ alkoxy, C₁-C₆alkoxycarbonyl, C₂-C₆ alkanoyl, carbamoyl and N—C₁-C₁₀ carbamoyl; or astraight-chain saturated C₁-C₉ aliphatic group, a straight-chainunsaturated C₁-C₉ aliphatic group, a branched saturated C₁-C₉ aliphaticgroup or a branched unsaturated C₁-C₉ aliphatic groups, each of whichgroups may optionally be substituted with the above-mentioned group,

[0305] R⁶⁰ represents a group selected from the group consisting ofhydrogen, halogen, optionally protected hydroxyl, N—C₁-C₆alkylsulfonylamino, C₁-C₆ alkoxy, C₁-C₆ alkoxycarbonyl, C₂-C₆ alkanoyl,carbamoyl and N—C₁-C₁₀ carbamoyl; or a straight-chain saturated C₁-C₉aliphatic group, a straight-chain unsaturated C₁-C₉ aliphatic group, abranched saturated C₁-C₉ aliphatic group or a branched unsaturated C₁-C₉aliphatic groups, each of which groups may optionally be substitutedwith the above-mentioned group,

[0306] R⁷ is as defined before,

[0307] R³⁰ and R⁴⁰ are the same or different, and represent

[0308] (1) groups selected from the group consisting of theaforementioned series of groups E provided that amino, carboxyl andhydroxyl may optionally be protected,

[0309] (2) groups selected from the group consisting of straight-chainsaturated C₁-C₉ aliphatic groups, straight-chain unsaturated C₁-C₉aliphatic groups, branched saturated C₁-C₉ aliphatic groups and branchedunsaturated C₁-C₉ aliphatic groups, each of which groups may optionallybe substituted with the above-mentioned group,

[0310] (3) (3-1) aryl groups; (3-2) mono- to tricyclic C₇-C₁₅ aromaticcarbocyclic groups selected from the group consisting ofacenaphthylenyl, adamantyl, anthryl, indenyl, norbornyl and phenanthryl;(3-3) 5- or 6-membered heterocyclic groups selected from the groupconsisting of the aforementioned series of groups A; (3-4) monocyclic totricyclic aromatic heterocyclic groups having per one ring 1 to 5 heteroatoms selected from the group consisting of nitrogen atoms, oxygen atomsand sulfur atoms, selected from the group consisting of theaforementioned series of groups B; or (3-5) straight-chain saturatedC₁-C₉ aliphatic groups, straight-chain unsaturated C₁-C₉ aliphaticgroups, branched saturated C₁-C₉ aliphatic groups or branchedunsaturated C₁-C₉ aliphatic groups, each of which groups may optionallybe substituted with the above-mentioned aryl group, aromatic carbocyclicgroup, heterocyclic group or aromatic heterocyclic group,

[0311] each of which groups (3-1) to (3-5) may optionally have one ormore substituents selected from the group consisting of theaforementioned series of groups C provided that amino, carboxyl,hydroxyl, N-amino C₁-C₁₀ alkylcarbamoyl and amino C₁-C₆ alkoxycarbonylmay be protected, or

[0312] (4) R³⁰ and R⁴⁰ combine together to form a straight-chainsaturated C₁-C₉ aliphatic group, a straight-chain unsaturated C₁-C₉aliphatic group, a branched saturated C₁-C₉ aliphatic group, a branchedunsaturated C₁-C₉ aliphatic group, a 5- or 6-membered saturatedcarbocyclic group or a 5- or 6-membered unsaturated carbocyclic group,

[0313] L₁ represents a hydrogen atom, a protective group for carboxylgroups, a protective group for amino groups, or a resin carrier of acarboxyl group or an amino group in peptide solid phase synthesis,

[0314] X₁₀ represents an oxygen atom, a sulfur atom or a group NR⁵⁰(wherein R⁵⁰ is as defined above)],

[0315] and the protective group of amino groups, the protective group ofhydroxy groups or the protective group of carboxyl groups [specifically,the protective groups when Y₁₀ (namely R⁵⁰) or L₁ has the protectivegroup of amino groups, the protective group of hydroxy groups or theprotective group of carboxyl groups] is removed if needed (when L₁ is aprotective group for amino groups, R⁵⁰ only represents a straight-chainor branched and saturated or unsaturated C₁-C₉ aliphatic group) to forma compound represented by the general formula [IV′]

[0316] [wherein, Y₁ represents an oxygen atom, a group NR⁵ or a groupCR⁶R⁷ (wherein, R⁵, R⁶ and R⁷ are as defined before), and R⁰, R¹⁰, R²⁰,R³⁰, R⁴⁰, L₁, X₂, X₁₀ and Z are as defined above).

[0317] The compounds represented by the general formula [IV′] are in anequilibrium state with compounds represented by the general formula [V′]

[0318] (wherein, R⁰, R¹⁰, R²⁰, R³⁰, R⁴⁰, L₁, X₂, X₁₀, Y₁ and Z are asdefined above). The compounds of the general formula [IV′] and thecompounds of the general formula [V′] are useful as intermediates forpreparation of the compounds of the general formula [I] of theinvention, and when they are used in reactions, they are usually used asan equilibrium mixture.

[0319] As resin carriers for carboxyl groups or amino groups in solidphase synthesis of peptides, polyethylene-divinylbenzene copolymers,polystyrene-divinylbenzene copolymers, etc. can for example bementioned. Resins comprising these polymers having inserted therein apolyethylene glycol can also be used. Among them, p-benzyloxybenzylalcohol resins (Wang™ Resin) are preferred as resin carriers forcarboxyl groups, and Trityl Chloride Resins are preferred as resincarriers for amino groups.

[0320] Reagents used in reactions can suitably be increased or decreaseddepending on the starting compounds and reaction conditions. Usually,the reaction between a carboxylic acid or thiocarboxylic acid of thegeneral formula [II] and an amine derivative of the general formula[III] can be carried out in a dehydrated inert organic solvent, ifneeded in the presence of a base, a condensation assistant and/or acondensing agent, at −100° C. to the boiling point of the solvent,preferably 0 to 30° C. for 0.5 to 96 hours, preferably 3 to 24 hours.Then, when the condensed compound has the protective groups for aminogroups, protective groups for hydroxy groups or protective groups forcarboxyl groups, the protective groups are suitably be removed tocomplete the reactions.

[0321] As inert organic solvents used in the reactions are notparticularly limited so long as the reactions are not badly influencedthereby, but specifically, there can for example be mentioned methylenechloride, chloroform, 1,2-dichloroethane, trichloroethane,N,N-dimethylformamide, ethyl acetate, methyl acetate, acetonitrile,acetic anhydride, methyl alcohol, ethyl alcohol, benzene, xylene, water,acetic acid, toluene, 1,4-dioxane. tetrahydrofuran, etc., and in view ofensuring suitable reaction temperature, methylene chloride, chloroform,1,2-dichloroethane, acetonitrile, N,N-dimethylformamide, 1,4-dioxane,toluene, etc. are preferred.

[0322] As bases used in the reaction, there can for example be mentionedtertiary aliphatic amines such as trimethylamine, triethylamine,N,N-diisopropylethylamine, N-methylmorpholine, N-methylpyrrolidine,N-methylpiperidine, N,N-dimethylaniline1,8-diazabicyclo[5.4.0]undec-7-ene (DBU) and1,5-azabicyclo[4.3.0]non-5-ene (DBN); aromatic amines such as pyridine,4-dimethylaminopyridine, picoline, lutidine, quinoline and isoquinoline;alkali metals such as metallic potassium, metallic sodium and metalliclithium; alkali metal hydrides such as sodium hydride and potassiumhydride; alkylated alkali metals such as butyllithium; alkali metalalkoxides such as potassium tert-butoxide, sodium ethoxide and sodiummethoxide; alkali metal hydroxides such as potassium hydroxide andsodium hydroxide; alkali metal carbonates such as potassium carbonate,etc., and preferred among them are tertiary aliphatic amines, andparticularly preferred are triethylamine, N,N-diisopropylethylamine,etc.

[0323] As condensation assistants used in the reaction, there can forexample be mentioned N-hydroxybenzotriazole hydrate,N-hydroxysuccinimide, N-hydroxy-5-nobornene-2,3-dicarboxyimide,3-hydroxy-3,4-dihydro-4-oxo-1,2,3-benzotriazole, etc., and preferredamong them are N-hydroxybenzotriazole, etc.

[0324] Condensing agents used in the reaction, there can for example bementioned thionyl chloride, N,N-dicyclohexylcarbodiimide,1-methyl-2-bromopyridium iodide, N,N′-carbonyldiimidazole,diphenylphosphoryl chloride, diphenylphosphoryl azide,N,N′-disuccinimidyl carbonate, N,N′-disuccinimidyl oxalate,1-ethyl-3-(3-dimethylamino-propyl)carbodiimide hydrochloride, ethylchloroformate, isobutyl chloroformate,benzotriazo-1-lyl-oxy-tris(dimethylamino)phosphoniumhexafluorophosphate, etc., and preferred among them areN,N-dicyclohexylcarbodiimide,1-ethyl-3-(3-dimethylaminopropyl)carbodiimide hydrochloride, ethylchloroformate, isobutyl chloroformate, etc.

[0325] Reagents used in the reaction can suitably be incresed ordecreased depending on the starting compounds and the reactionconditions, but usually, 0.02 to 50 equivalents. preferably 0.2 to 2equivalents of an amine derivative of the general formula [III], 1 to 50equivalents, preferably 3 to 5 equivalents of a base, 1 to 50equivalents, preferably 1 to 5 equivalents of a condensation assistantand/or 1 to 50 equivalents, preferably 1 to 5 equivalents of acondensing agent are used based on a carboxylic acid or thiocarboxylicacid of the general formula [II]. The base, condensation assistant andcondensing agent can each be used alone or a combination of two or more.

[0326] (Second Step)

[0327] Next, an equilibrium mixture of a compound represented by thegeneral formula [IV′]

[0328] (wherein, R⁰, R¹⁰, R²⁰, R³⁰, R⁴⁰, L₁, X₂, X₁₀, Y₁ and Z are asdefined above) and a compound represented by the general formula [V′]

[0329] (wherein, R⁰, R¹⁰, R²⁰, R³⁰, R⁴⁰, L₁, X₂, X₁₀, Y₁ and Z are asdefined above) is reacted with an acid in an inert organic solvent toform a compound represented by the general formula [VIII′]

[0330] (wherein, R⁰, R¹⁰, R²⁰, R³⁰, R⁴⁰, X₂, X₁₀, Y₁ and Z are asdefined above), and the protective groups are suitably removed to form acompound represented by the general formula [I′]

[0331] (wherein, R, R¹, R², R³, R⁴, X₁, X₂, Y₁ and Z are as definedabove), namely a compound of the general formula [I-1], a compound ofthe general formula [I-2] or a compound of the general formula [I-3] ora pharmaceutically acceptable salt thereof. When L₁ is a resin carrierfor carboxyl groups or amino groups in solid phase synthesis ofpeptides, by removing the resin carrier after the reaction with theacid, a compound of the general formula [I-1] or a compound of thegeneral formula [I-2] can be prepared. A compound of the general formula[I′] wherein X₁ is NR⁵ (wherein, R⁵ is as defined before) or Y₁ is NR⁵or CR⁶R⁷ (wherein, R⁵, R⁶ and R⁷ are as defined before) can usually beprepared using a starting compound having such a substituent, but adesired compound of the general formula [I′] can also be prepared bypreparing a compound of the general formula [VIII′] wherein X₁₀ is anoxygen atom or NH or Y₁ is NH or CHR⁷ (wherein, R⁷ is as definedbefore), and then, by conventional methods, replacing the oxygen atomwith NR⁵ (wherein, R⁵ is as defined before) or introducing R⁵ or R⁶(wherein, R⁵ and R⁶ are as defined before) in NH or CHR⁷ (wherein, R⁷ isas defined before). As the introduction methods, there can for examplebe mentioned a reaction wherein a carbonyl group is reacted withmethoxylamine hydrochloride to convert it to a methoxime group, areaction wherein a group CHR⁷ (wherein, R⁷ is as defined before) isreacted with an alkyl metal reagent and then the reaction product istreated with an alkyl halide to give a group CR⁶R⁷ (wherein, R⁶ and R⁷are as defined before), etc.

[0332] Reagents used in the reaction can suitably be increased ordecreased depending on the starting compounds and the reactionconditions Usually, the reaction can be carried out by reacting anequilibrium mixture between a compound of the general formula [IV] and acompound of the general formula [V] with a catalytic amount of an acidin a dehydrated inert organic solvent, at −100° C. to the boiling pointof the solvent, preferably 0 to 30° C. for 0.5 to 96 hours, preferably 2to 24 hours. Then, when the protective groups for amino groups exist,they are suitably removed to complete the reaction.

[0333] As to protective groups protecting functional groups other thanL₁, N-protective groups, protective groups for carboxyl groups,protective groups for hydroxy groups, etc. can simultaneously be removedby suitably selecting a method to remove protective groups, reactionconditions, etc. It is also possible to selectively remove one ofN-protective groups, protective groups for carboxyl groups, protectivegroups for hydroxy groups. The order of removal of the protective groupsis not particularly limited.

[0334] As protective groups for hydroxyl groups, there can for examplebe mentioned lower alkylsilyl groups such as tert-butyldimethylsilyl andtert-butyldiphenylsilyl; lower alkoxymethyl groups such as methoxymethyland 2-methoxyethoxymethyl; aralkyl groups such as benzyl andp-methoxybenzyl; acyl groups such as formyl and acetyl, etc., andtert-butyldimethylsilyl, acetyl, etc. are preferred.

[0335] As protective groups for amino groups, there can for example bementioned aralkyl groups such as benzyl and p-nitrobenzyl; acyl groupssuch as formyl and acetyl; lower alkoxycarbonyl groups such asethoxycarbonyl and tert-butoxycarbonyl; aralkyloxycarbonyl groups suchas benzyloxycarbonyl and p-nitrobenzyloxycarbonyl, etc., andp-nitrobenzyl, tert-butoxycarbonyl, benzyloxycarbonyl, etc. arepreferred.

[0336] As protective groups for carboxyl groups, there can for examplebe mentioned lower alkyl groups such as methyl, ethyl and tert-butyl;aralkyl groups such as benzyl and p-methoxybenzyl, etc., and methyl,ethyl, tert-butyl, benzyl, etc. are preferred.

[0337] Methods for removing the protective groups are varied dependingon their kinds and the stability of compounds, but removal of theprotective groups can be carried out by methods described in literatures(e.g., see “Protective Groups in Organic Synthesis” written by T. W.Green, John Wiley & Sons Co. (1981)) or by a little modified onesthereof, for example by solvolysis using an acid or a base, chemicalreduction using a metal hydride complex or the like, catalytic reductionusing palladium-carbon catalysts, Raney nickel catalysts or the like,etc.

[0338] Inert organic solvents used in the invention are not particularlylimited so long as the reaction is not badly influenced, and theaforementioned inert organic solvents can be mentioned.

[0339] As acids used in the invention, there can for example bementioned inorganic acids such as hydrochloric acid, nitric acid,hydrobromic acid, sulfuric acid, hydrofluoric acid and perchloric acid;Lewis acids such as trifluoroboric acid; sulfonic acids such asp-toluenesulfonic acid, trifluoromethanesulfonic acid andmethanesulfonic acid; organic acids such as formic acd, trifluoroaceticacid and acetic acid, etc., and Lewis acids such as trifluoroboric acid,and organic acids such as trifluoroacetic acid, etc. are preferred.

[0340] After completion of the reaction, by purifying the product byusual known methods, a compound of the general formula [I-1], [I-2] or[I-3] can be obtained. Isolation and purification of the compound of thegeneral formula [I-1], [I-2] or [I-3] can be carried out by knownseparation means such as extraction with solvents, recrystallization andchromatography.

[0341] Preparation Process B

[0342] This preparation process is for preparation of the compounds ofthe general formula [I-4] of the invention, namely the compounds of thegeneral formula [I] wherein Y is a sulfur atom.

[0343] An equilibrium mixture between a compound represented by thegeneral formula [IV″]

[0344] (wherein, Y₂ represents an oxygen atom, L₂ represents a hydrogenatom, and R⁰, R¹⁰, R²⁰, R³⁰, R⁴⁰, X₂, X₁₀ and Z are as defined before)

[0345] and a compound represented by the general formula [V″]

[0346] (wherein, R⁰, R¹⁰, R²⁰, R³⁰, R⁴⁰, L₂, X₂, X₁₀, Y₂ and Z are asdefined before) is reacted with a sulfurizing agent to form anequilibrium mixture between a compound represented by the generalformula [VI″]

[0347] (wherein, Y₃ represents a sulfur atom, and R⁰, R¹⁰, R²⁰, R³⁰,R⁴⁰, L₂, X₂, X₁₀ and Z are as defined before)

[0348] and a compound represented by the general formula [VII″]

[0349] (wherein, R⁰, R¹⁰, R²⁰, R³⁰, R⁴⁰, L₂, X₂, X₁₀, Y₃ and Z are asdefined before), and then, the formed equilibrium mixture is reactedwith an acid in an inert organic solvent at a temperature of from roomtemperature to the boiling point of the solvent to form a compoundrepresented by the general formula [VIII″]

[0350] (wherein, R⁰, R¹⁰, R²⁰, R³⁰ , R⁴⁰, X₂, X₁₀, Y₃ and Z are asdefined before), and the protective groups are suitably removed toobtain a compound represented by the general formula [I″]

[0351] (wherein, R, R¹, R², R³, R⁴, X₁, X₂, Y₃ and Z are as definedbefore) or a pharmaceutically acceptable salt thereof.

[0352] Reagents used in the reaction can suitably be increased ordecreased depending on the starting compounds and the reactionconditions. Usually, an equilibrium mixture between a compound of thegeneral formula [IV″] and a compound of the general formula [V″] isreacted with a sulfurizing agent in a dehydrated inert organic solventat −100° C. to the boiling point of the solvent, preferably 0 to 30° C.for 0.5 to 96 hours, preferably 1 to 12 hours to form an equilibriummixture between a compound of the general formula [VI″] and a compoundof the general formula [VII″], and then reaction is carried out in thesame manner as in the second step in Preparation process A to form acompound of the general formula [VIII″], and then after suitable removalof the protective groups, purification is carried out according tosuitable methods to obtain a compound of the general formula [I″],namely a compound of the general formula [I-4]. Isolation andpurification of the compound of the general formula [I-4] or the saltthereof from the reaction mixture can be carried out by known separationmeans such as extraction with solvents, recrystallization andchromatography, as in Preparation process A.

[0353] A carboxylic acid or thiocarboxylic acid of the general formula[II] is known in literatures, or can be prepared by reacting an arylhalide represented by the general formula [IX]

R⁰—X   [IX]

[0354] (wherein, X represents a halogen atom, and R⁰ is as definedbefore) with metallic magnesium in a dehydrated etherial solvent such asdiethyl ether or tetrahydrofuran at from a low temperature to theboiling point of the solvent to prepare a Grignard's reagent, and thenreacting the Grignard's reagent with an optionally substituted acidanhydride in a dehydrated inert organic solvent at a low temperature toroom temperature.

[0355] A compound of the general formula [II] can also be prepared bysubjecting an arene compound of the general formula [X]

R^(O)—H   [X]

[0356] (wherein, R⁰ is as defined before) and a substituted orunsubstituted acid anhydride to Friedel-Crafts' acylation reaction, ifnecessary in the presence of an aforementioned acid.

[0357] Compounds of the general formula [III] are known in literatures,or are amino acids or amino acid derivatives derivable from the aminoacids, represented by the general formula [III]

[0358] (wherein, Y₄ represents an oxygen atom, L3 represents a hydrogenatom, a protective group for carboxy groups or a resin carrier ofcarboxyl groups in solid phase synthesis of peptides, and R³⁰, R⁴⁰ andX₁ are as defined before).

[0359] A compounds of the general formula [III] can be prepared byreacting an amino acid, or a carboxylic acid or thiocarboxylic acid,which is an amino acid derivative derivable from the amino acid,represented by the general formula [XI]

[0360] (wherein, L₄ represents a hydrogen atom or a protective group forcarboxyl groups, R⁹⁰ represents a hydrogen atom or a protective groupfor amino groups, and R³⁰, R⁴⁰, X₁ and Y₄ are as defined before)

[0361] with an amine derivative represented by the general formula [XII]

R⁵⁰NH—R⁸⁰   [XII]

[0362] (wherein, R⁸⁰ represents a protective group for amino groups or aresin carrier of amino groups in solid phase synthesis of peptides, andR⁵⁰ is as defined before), and then, in the case of R⁹⁰ being aprotective group for amino groups, removing the protective group foramino groups.

[0363] A compounds of the general formula [III] can also be prepared byreacting an amino acid or amino acid derivative represented by thegeneral formula [XIII]

[0364] (wherein, Y₅ represents an oxygen atom or a nitrogen atom, L₅represents a protective group for carboxyl groups, a hydrogen atom or aprotective group for amino groups, and R³⁰, R⁴⁰, R⁹⁰ and X₁ are asdefined before) with a Grignard's reagent represented by the generalformula [XIV]

R⁶⁰R⁷CH—MgX   [XIV]

[0365] (wherein, X represents a halogen atom, and R⁶⁰ and R⁷ are asdefined before), and then, in the case of R⁹⁰ being a protective groupfor amino groups, removing the protective group for amino groups.

[0366] For specifically demonstrating the usefulness of the invention,the compound of Example 1002 was used, and after administration of thecompound, an influence of the compound on the GLP-1 concentration in theplasma was examined. The test method and the results are shown below.

[0367] (Test Method)

[0368] Male Wistar rats (9 weeks old, n=6) bred under the condition offree access to food and water were fasted overnight before the test, anda suspension of a test compound in 1% carboxymethylcellulose solutionwas administered. As a control group, 1% carboxymethylcellulose solutionwas orally administered to the rats. Thirty minutes after theadministration of the test compound, blood was withdrawn, and subjectedto centrifugation to separate the plasma. The GLP-1 concentration in theplasma was determined by the radioimmunoassay method using commerciallyavailable anti GLP-1 antibody (Cosmo Co., Ltd.). The obtained valueswere analyzed using Student T test, and the statistical significantdifference was calculated. The results are shown in the following Table46.

[0369] =Test Results= TABLE 46

[0370] As apparent from the above result, at 30 minutes after theadministration, in the group to which 30 mg/kg of the compound wasadministered, significantly higher GLP-1 concentration in the blood(plasma) was observed in comparison with the control group. From theresult, it is demonstrated that the compounds of the invention have anactivity to be able to achieve high GLP-1 concentration in the blood ofrats.

[0371] Since the compounds of the invention have an activity to bringabout high GLP-1 concentration in the blood, they are useful as drugsfor treating diabetes, prophylactic agents for chronic complications ofdiabetes, or drugs against obesity.

[0372] The compounds of the general formula [I] of the invention can beused as an effective ingredient in drugs, particularly agents fortreating diabetes, prophylactic agents for chronic complications ofdiabetes, or drugs against obesity. The compounds of the invention inmedicaments, particularly agents for treating diabetes, prophylacticagents for chronic complications of diabetes, or drugs against obesity,include pharmaceutically acceptable conventional ones, for example,compounds represented by the general formula [I]

[0373] (wherein, R, R¹, R², R³, R⁴, X₁, X₂, Y and Z are as definedbefore), pharmaceutically acceptable esters or salts in carboxyl groupson R, R¹, R², R³ or R⁴, pharmaceutically acceptable salts in hydroxylgroups on R, R¹, R², R³ or R⁴, pharmaceutically acceptable salts inamino groups on R, R¹, R¹, R³ or R⁴.

[0374] As salts in the carboxyl groups or the hydroxyl groups, there canfor example be mentioned alkali metal salts such as sodium salts andpotassium salts, alkaline earth metal salts such as calcium salts andmagnesium salts.

[0375] As acid addition salts in the amino groups, there can for examplebe mentioned inorganic salts such as hydrochlorides, sulfates, nitrates,phosphates, carbonates, bicarbonates and perchlorates, organic acidsalts such as acetates, propionates, lactates, maleates, flimarates,tartrates, malates, citrates and ascorbates, sulfonates such asmethanesulfonates, isethionates, benzenesulfonates andtoluenesulfonates, acidic amino acid salts such as aspartates andglutamates, etc.

[0376] When compounds of the invention are used as agents for treatingdiabetes, prophylactic agents for chronic complications of diabetes, ordrugs against obesity, they can also be used as their pharmacologicallyacceptable salts. As typical examples of pharmacologically acceptablesalts, there can for example be mentioned salts with alkali metals suchas sodium and potassium.

[0377] Preparation of pharmacologically acceptable salts of compounds ofthe invention can be carried out by appropriately combining processesusually used in the field of organic synthetic chemistry. Specifically,there can be mentioned subjecting solutions of compounds of theinvention in a free form to acidimetry using an alkali solution, etc.

[0378] As dosage forms of the compounds of the invention when used asagents for treating diabetes, prophylactic agents for chroniccomplications of diabetes, or drugs against obesity, various forms canbe selected, and there can for example be mentioned oral agents such astablets, capsules, powders, granules and liquid medicines, sterilizedliquid parenteral agents such as solutions and suspensions, etc.

[0379] Solid pharmaceutical preparations such as tablets, capsules,granules and powders can be prepared using compounds of the inventionalone, but can also be prepared further using suitable additives. As thesuitable additives, there can be mentioned conventional additives, forexample, sugars such as lactose and glucose, starches such as corn,wheats and rices, fatty acids such as stearic acid, inorganic salts suchas sodium metasilicate, magnesium aluminate and anhydrous calciumphosphate, synthetic macromolecules such as polyvinylpyrrolidone andpolyalkylene glycols, fatty acid salts such as calcium stearate andmagnesium stearate, alcohols such as stearyl alcohol and benzyl alcohol,synthetic cellulose derivatives such as methylcellulose,carboxymethylcellulose, ethylcellulose and hydroxypropylmethylcellulose,and further, water, gelatin, talc, vegetable oils, gum arabic, etc.

[0380] These solid pharmaceutical preparations such as tablets,capsules, granules and powders can contain, generally 0.1 to 100% byweight, preferably 5 to 100% by weight of the effective ingredient.Liquid pharmaceutical preparations can be prepared as forms ofsuspensions, syrups, injections, etc. using suitable additives usuallyused in liquid pharmaceutical preparations, such as water, alcohols orvegetable oils including soybean oil, peanut oil and sesame oil.Particularly, as solvents suitable in parenteral administration, therecan for example be mentioned distilled water for injection, aqueouslidocaine hydrochloride solution (for intramuscular injection),physiological saline, aqueous glucose solution, ethanol, liquids forintravenous injection (e.g. aqueous solutions of citric acid, sodiumcitrate, etc.), electrolyte solutions (e.g., for intravenous injectionby drip, for intravenous injection), etc., or their mixed solutions.

[0381] Liquid pharmaceutical preparations such as suspensions and syrupsfor oral administration can contain 0.5 to 10% by weight of an effectiveingredient.

[0382] The actually preferred dose of the compounds of the invention canappropriately be increased or decreased depending on kinds of compoundsused, kinds of compositions prepared, application frequency, particularsites to be treated, and states of diseases of patients. For example,the dose of each compound per day and per one adult is 0.1 to 1,000 mgin the case of oral administration, and 0.01 to 500 mg in the case ofparenteral administration. The frequency of administration is varieddepending on administration methods and symptoms, but the administrationcan be made in a time or in divided 2 to 5 times.

BEST MODE FOR CARRYING OUT THE INVENTION

[0383] The invention is further specifically described below accordingto examples, but the invention is not limited thereby at all.

[0384] In thin layer chromatography in examples, Silicagel 60F₂₄₅(Merck)was used as plates, and UV detectors as detection means. Wakogel™ C-300(Wako Pure Chemical) was used as silica gel for columns, and LC-SORB™SP-B-ODS (Chemco) or YMC-GEL™ ODS-AQ 120-S50 (Yamamura ChemicalLaboratory) as silica gel for reverse-phase columns.

[0385] i-Bu: isobutyl group, n-Bu: n-butyl group, t-Bu: t-butyl group

[0386] Me: methyl group, Et: ethyl group, Ph: phenyl group

[0387] i-Pr: isopropyl group, n-Pr: n-propyl group, CDCl₃: heavychloroform

[0388] methanol-d₄: heavy methanol, DMSO-d₆: heavy dimethylsulfoxide

EXAMPLES Example 1001

[0389] 9b-(2-Methoxyphenyl)-3-(1-methylethyl)[1,3]oxazolo[2-3-a]isoindole-2,5(3H,9bH)-dione (compound ofR¹:H;R²:H;R³:i-Pr;R⁴:H;Z:Ph;R:2-MeO-Ph in the following general formula[I-1])

[0390] A solution in tetrahydrofuran (17 ml) of a Grignard's reagentprepared from magnesium (120 mg, 5.1 mmol) and 2-bromoanisole (0.55 ml,4.4 mmol) was added dropwise to a solution of phthalic anhydride (500mg, 3.4 mmol) in tetrahydrofuran (12 ml) in an atmosphere of nitrogen at−70° C. over a period of 10 minutes. The reaction mixture was stirred at−70° C. for 2.5 hours, and aqueous saturated ammonium chloride solutionwas added. The mixture was extracted with ethyl acetate, and the organiclayer was washed with aqueous saturated sodium chloride solution, driedand concentrated under reduced pressure to obtain crude2-(2-methoxybenzoyl)benzoic acid (770 mg, yield: 90%).

[0391] 1-Hydroxybenzotriazole hydrate (490 mg, 3.6 mmol) and1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (690 mg, 3.6mmol) were added to a solution of 2-(2-methoxybenzoyl)benzoic acid (750mg, 3.0 mmol), D-valine methyl ester hydrochloride (550 mg, 3.4 mmol)and triethylamine (1.26 ml, 9.1 mmol) in methylene chloride (40 ml)under ice cooling, and the reaction mixture was stirred at roomtemperature for 3 hours. Aqueous saturated ammonium chloride solutionwas added to the reaction mixture, and the mixture was extracted withchloroform. The organic layer was washed with aqueous saturated sodiumchloride solution, dried and concentrated under reduced pressure. Theresulting residue was dissolved in methanol (15 ml), 4N aqueous sodiumhydroxide solution (8 ml) was added, and the reaction mixture wasstirred at room temperature for 12 hours and concentrated under reducedpressure. 1N Aqueous hydrochloric acid solution (40 ml) and ethylacetate were added to the resulting residue, and the organic layer wasdried and concentrated under reduced pressure. The resulting unpurifiedcarboxylic acid was dissolved in methylene chloride (6 ml),trifluoroacetic acid (5 ml) was added, and the reaction mixture wasstirred at room temperature for 2 hours. The reaction mixture wasconcentrated under reduced pressure, the residue was subjected threetimes to azeotropic distillation with toluene, and the mixture wasconcentrated under reduced pressure. The resulting residue was purifiedby silica gel column chromatography (hexane: ethyl acetate=3:2) toobtain the captioned compound (470 mg, yield: 46%) as light yellow oilymatter).

[0392]¹HNMR(CDCl₃) δ:0.85(3H,d,J=6.6 Hz),1.10(3H,d,J=6.6Hz),1.56-1.66(1H,m),3.48(3H,s),4.17(1H,d,J=10.5 Hz),6.83(1H,d,J=7.8Hz),7.04(1H,t,J=7.8 Hz),7.34-7.36(1H,m), 7.38(1H,t,J=7.8Hz),7.53-7.60(2H,m),7.75(1H,d,J=7.8 Hz), 7.89-7.92(1H,m)FAB-MS(m/e):338[M+H]⁺

[0393] In the same manner as in Example 1001, compounds of Examples 1002to 1222. 1413, and 1427 to 1439 corresponding to the compound numbers ofthe compounds of the general formula [I-1] in the aforementionedcompound lists were obtained. Physical constants of these compounds areshown below.

Example 1002

[0394] (R¹:H;R²:H;R³:i-Pr;R⁴:H;Z:Ph;R:Ph)

[0395]¹HNMR(CDCl₃) δ:0.92(3H,d,J=6.6 Hz), 1.11 (3H,d,J=6.7Hz),1.56-1.67(1H,m),4.22(1H,d, J=9.8 Hz),7.33(1H,dd,J=2.7,5.8Hz),7.37-7.62(7H,m),7.92(1H,dd,J=2.8,5.8 Hz) FAB-MS(m/e):308[M+H]⁺

Example 1003

[0396] (R¹:H;R² :H;R³:i-Pr;R⁴:H;Z:Ph;R:2-NH₂-Ph)

[0397] ESI-MS(m/e):323[M+H]⁺

Example 1004

[0398] (R¹:H;R²:H;R³:i-Pr;R⁴:H;Z:Ph;R:4-F-Ph)

[0399] ESI-MS(m/e):326[M+H]⁺

Example 1005

[0400] (R¹:H;R²:H;R³:i-Pr;R⁴:H;Z:Ph;R:4-Et₂N-Ph)

[0401] ESI-MS(m/e):379[M+H]⁺

Example 1006

[0402] (R¹:H;R² :H;R³:i-Pr;R⁴:H;Z:Ph;R:4-Cl-Ph)

[0403]¹HNMR(CDCl₃) δ:0.92(3H,d,J=6.6 Hz),1.12(3H,d,J=7.2Hz),1.54-1.70(1H,m),4.21(1H, d,J=9.4 Hz),7.32(1H,ddd,J=0.6,2.4,5.4Hz),7.37(2H,d,J=9.0 Hz),7.43(2H,d,J=9.0 Hz),7.58-7.62(2H,m),7.91(1H,ddd,J=0.6,2.4,5.4 Hz) FAB-MS(m/e):342[M+H]⁺

Example 1007

[0404] (R¹:H;R²:H;R³:i-Pr;R⁴:H;Z:Ph;R:4-HO-Ph)

[0405]¹HNMR(CDCl₃) δ:0.93(3H,d,J=6.7 Hz),1.11(3H,d,J=6.7Hz),1.59-1.75(1H,m),4.19(1H,d,J=9.9 Hz),6.85(2H,d,J=8.8Hz),7.33-7.37(3H,m),7.57-7.60(2H,m),7.88-7.91(1H,m)FAB-MS(m/e):324[M+H]⁺

Example 1008

[0406] (R¹:H;R²:H;R³:i-Pr;R⁴:H;Z:Ph;R:3-MeO-Ph)

[0407]¹HNMR(CDCl₃) δ:0.96(3H,d,J=6.6 Hz), 1.12(3H,d,J=6.6Hz),1.63-1.71(1H,m),3.79(3H,s),4.21(1H,d,J=9.9 Hz),6.90(1H,dd,J=1.4,8.0Hz),7.02(1H,d,J=1.4 Hz),7.08(1H,d, J=8.0 Hz),7.31(1H,t,J=8.0Hz),7.36-7.38(1H,m),7.56-7.62(2H,m),7.89-7.92(1H,m)FAB-MS(m/e):338[M+H]⁺

Example 1009

[0408] (R¹:H;R²:H;R³:i-Pr;R⁴:H;Z:Ph;R:3-HO-Ph)

[0409]¹HNMR(CDCl₃) δ:0.95(3H,d,J=6.6 Hz),1.12(3H,d,J=6.6Hz),1.67-1.72(1H,m),4.21(1H,d,J=9.9 Hz),6.85(1H,ddd,J=0.9,2.5,7.9Hz),6.97(1H,d,J=2.5 Hz),7.06(1H,dd,J=0.9,7.9 Hz),7.27(1H,t,J=7.9Hz),7.34-7.38(1H,m),7.54-7.62(2H,m),7.85-7.88(1H,m)FAB-MS(m/e):324[M+H]⁺

Example 1010

[0410] (R¹:H;R²:H;R³:i-Pr;R⁴:H;Z:Ph;R:3-NH₂-Ph)

[0411] ESI-MS(m/e):323[M+H]⁺

Example 1011

[0412] (R¹:H;R²:H;R³:i-Pr;R⁴:H;Z:Ph;R:4-MeO-Ph)

[0413]¹HNMR(CDCl₃) δ:0.93(3H,d,J=6.7 Hz),1.11(3H,d,J=6.7Hz),1.63-1.69(1H,m),3.82(3H,s),4.19(1H,d,J=9.9 Hz),6.89(2H,d,J=8.8Hz),7.32-7.37(1H,m),7.40(2H,d,J=8.8 Hz). 7.57-7.60(2H,m),7.89-7.92(1H,m) FAB-MS(m/e):338[M+H]⁺

Example 1012

[0414] (R¹:H;R²:H;R³:i-Pr;R⁴:H;Z:Ph;R:4-Me-Ph)

[0415]¹HNMR(CDCl₃) δ:0.94(3H,d,J=6.6 Hz),1.11(3H,d,J=6.7Hz),1.57-1.72(1H,m),2.36(3H,s),4.20(1H,d,J=10.0 Hz),7.22(1H,d,J=8.5Hz),7.32-7.36(1H,m),7.37(1H,d, J=8.5 Hz),7.55-7.61(2H,m),7.88-7.95(1H,m)FAB-MS(m/e):322[M+H]⁺

Example 1013

[0416] (R¹:H;R²:H;R³:i-Pr;R⁴:H;Z:Ph;R:3-Me-Ph)

[0417]¹HNMR(CDCl₃) δ:0.86(3H,d,J=6.7 Hz),1.03(3H,d,J=6.7Hz),1.52-1.60(1H,m),2.27(3H,s),4.13(1H,d,J=9.9Hz),7.09-7.20(4H,m,),7.20-7.29(1H,m),7.47-7.53(2H,m), 7.82-7.84 (1H,m)FAB-MS(m/e):322[M+H]⁺

Example 1014

[0418] (R¹:H;R²:H;R³:i-Pr;R⁴:H;Z:Ph;R:t-BuO₂CCH₂O-Ph)

[0419]¹HNMR(CDCl₃) δ:0.92(3H,d,J=6.7 Hz),1.10(3H,d,J=6.7Hz),1.47(9H,s),1.60-1.68(1H,m),4.19(1H,d,J=9.9Hz),4.52(2H,s),6.89(2H,d,J=8.8 Hz),7.40(2H,d,J=8.8 Hz), 7.32-7.91 (4H,m)FAB-MS(m/e):438[M+H]⁺

Example 1015

[0420] (R¹:H;R²:H;R³:i-Pr;R⁴:H;Z:Ph;R:HO₂CCH₂O-Ph)

[0421]¹HNMR(CDCl₃) δ:0.93(3H,d,J=6.6 Hz),1.11(3H,d,J=6.6Hz),1.60-1.70(1H,m),4.19(1H,d,J=9.9 Hz),4.69(2H,s),6.84(2H,d,J=9.0Hz),7.43(2H,d,J=9.0 Hz),7.31-7.92(4H,m) FAB-MS(m/e):382[M+H]⁺

Example 1016

[0422] (R¹:H;R²:H;R³:i-Pr;R⁴:H;Z:Ph;R:4-tBuO₂C(CH₂)₅O-Ph)

[0423]¹HNMR(CDCl₃) δ:0.94(3H,d,J=6.6 Hz),1.11(3H,d,J=6.6Hz),1.439-1.441(9H,m),1.49-1.84(7H,m),2.24(2H,t,J=7.2Hz),3.95(2H,t,J=6.4 Hz),4.19(1H,d,J=10.1 Hz),6.87(2H,d,J =8.4Hz),7.32-7.35(1H,m),7.38(2H,d,J=8.4 Hz),7.55-7.60(2H,m),7.88-7.91(1H,m)FAB-MS(m/e):494[M+H]⁺

Example 1017

[0424] (R¹:H;R²:H;R³:i-Pr;R⁴:H;Z:Ph;R:4-HO₂C(CH₂)₅O-Ph)

[0425]¹HNMR(CDCl₃) δ:0.83(3H,d,J=6.7 Hz),1.10(3H,d,J=6.7Hz),1.47-1.85(7H,m)2.39(2H,t,J=7.8 Hz),3.85(2H,t,J=7.2Hz),4.18(1H,d,J=10.7 Hz),6.87(2H,d,J=8.9 Hz),7.31-7.39(1H,m),7.39(2H,d,J=8.9 Hz),7.54-7.61(2H,m),7.87-7.92(1H,m)FAB-MS(m/e):438[M+H]⁺

Example 1018

[0426] (R¹:H;R²:H;R³:i-Pr;R⁴:H;Z:Ph;R:4-HO(CH₂)₃O-Ph)

[0427]¹HNMR(CDCl₃) δ:0.93(3H,d,J=6.7 Hz),1.11(3H,d,J=6.7 Hz),1.61-1.711(1H,m),2.04(2H, quintet,J=5.9 Hz),3.86(2H,t,J=5.9 Hz),4.12(2H,t,J=5.9Hz),4.20(1H,d,J=9.8 Hz),6.90(2H, d,J=8.8 Hz),7.32-7.91 (6H,m)FAB-MS(m/e):382[M+H]⁺

Example 1019

[0428] (R¹:H;R²:H;R³:i-Pr;R⁴:H;Z:Ph;R:4-HO(CH₂)₂O-Ph)

[0429]¹HNMR(CDCl₃) δ:0.95(3H,d,J=6.7 Hz),1.13(3H,d,J=6.7Hz),1.63-1.71(1H,m), 3.99(2H,t,J=4.4 Hz),4.11(2H,t,J=4.4Hz),4.22(1H,d,J=9.9 Hz),6.94(2H,d,J=8.9 Hz),7.29-7.93(6H,m)FAB-MS(m/e):368[M+H]⁺

Example 1020

[0430] (R¹:H;R²:H;R³:i-Pr;R⁴:H;Z:Ph;R:4-HOC(Me)₂(CH₂)₂O-Ph)

[0431]¹HNMR(CDCl₃) δ:0.95(3H,d,J=6.7 Hz),1.13(3H,d,J=6.7Hz),1.32(6H,s),1.61-1.68(1H,m),2.01(2H,t,J=6.4 Hz),4.19(2H,t,J=6.4Hz),4.21(1H,d,J=9.9 Hz),6.91 (2H,d,J=8.9H z),7.41(2H,d,J=8.9Hz),7.33-7.92(4H,m) FAB-MS(m/e):410[M+H]⁺

Example 1021

[0432] (R¹:H;R²:H;R³:i-Pr;R⁴:H;Z:Ph;R:4-PhCH₂O-Ph)

[0433]¹HNMR(CDCl₃) δ:0.94(3H,d,J=6.6 Hz),1.12(3H,d,J=6.6Hz),1.60-1.75(1H,m),4.20(1H,d, J=9.9 Hz),5.06(2H,s),6.98(2H,d,J=8.9Hz),7.33-7.92(11H,m) FAB-MS(m/e):414[M+H]⁺

Example 1022

[0434] (R¹:H;R²:H;R³:i-Pr;R⁴:H;Z:Ph;R:4-MeNHCOCH₂O-Ph)

[0435]¹HNMR(CDCl₃) δ:0.92(3H,d,J=6.7 Hz),1.11(3H,d,J=6.7Hz),1.60-1.68(1H,m),2.92(3H,d,J=5.1 Hz),4.20(1H,d,J=9.9Hz),4.50(2H,s),6.56-6.59(1H,m),6.93(2H,d,J=8.9 Hz),7.32-7.36(1H,m),7.45(2H,d,J=8.9 Hz),7.57-7.63(2H,m),7.90-7.93(1H,m)FAB-MS(m/e):395[M+H]⁺

Example 1023

[0436] (R¹:H;R²:H;R³:i-Pr;R⁴:H;Z:Ph;R:4-EtNHCOCH₂O-Ph)

[0437]¹HNMR(CDCl₃) δ:0.92(3H,d,J=6.7 Hz),1.11(3H,d,J=6.7Hz)1.18(3H,t,J=7.3 Hz), 1.60-1.70(1H,m),3.40(2H,dt,J=5.9,7.3Hz),4.20(1H,d,J=9.8 Hz),4.48(2H,s),6.53(1H,brs), 6.93(2H,d,J=9.0Hz),7.31-7.92(6H,m) FAB-MS(m/e):409[M+H]⁺

Example 1024

[0438] (R¹:H;R²:H;R³:i-Pr;R⁴:H;Z:Ph;R:4-n-PrNHCOCH₂O-Ph)

[0439]¹HNMR(CDCl₃) δ:0.89-0.94(6H,m),1.12(3H,d,J=7.2Hz),1.53-1.66(3H,m),3.32 (2H,dt, J=7.2 Hz),4.21(1H,d,J=9.9Hz),4.50(2H,s),6.53(1H,br),6.95(2H,d,J=8.9 Hz),7.31-7.93(6H,m)FAB-MS(m/e):414[M+H]⁺

Example 1025

[0440] (R¹:H;R²:H;R³:i-Pr;R⁴:H;Z:Ph;R:4-n-BuNHCOCH₂O-Ph)

[0441]¹HNMR(CDCl₃) δ:0.92(3H,t,J=7.2 Hz),0.92(3H,d,J=6.6Hz),1.11(3H,d,J=6.6 Hz),1.26-1.40(2H,m),1.48-1.70(3H,m),3.35(2H,q,J=6.8Hz),4.21(1H,d,J=9.8 Hz),4.49(2H,s),6.52-6.53(1H,m),6.94(2H,d,J=9.0Hz),7.31-7.36(1H,m),7.45(2H,d,J=9.0 Hz),7.57-7.63(2H,m),7.88-7.93(1H,m)FAB-MS(m/e):437[M+H]⁺

Example 1026

[0442] (R¹:H;R²:H;R³:i-Pr;R⁴:H;Z:Ph;R:4-CH₂═CHCH₂NHCOCH₂O-Ph)

[0443]¹HNMR(CDCl₃) δ:0.93(3H,d,J=6.7 Hz),1.13(3H,d,J=6.7Hz),1.61-1.67(1H,m),3.98-4.02(2H,m),4.22(1H,d,J=9.8Hz),4.54(2H,s),5.82-5.91(1H,m),6.65(1H,br),6.96(2H,d, J=8.9Hz),7.33-7.94(6H,m) ESI-MS(m/e):421[M+H]⁺

Example 1027

[0444] (R¹:H;R²:H;R³:i-Pr;R⁴:H;Z:Ph;R:4-Me(CH₂)₉NHCOCH₂O-Ph)

[0445]¹HNMR(CDCl₃) δ:0.87(3H,t,J=6.5 Hz),0.92(3H,d,J=6.6Hz),1.11(3H,d,J=6.6 Hz),1.25-1.67(7H,m),3.33(2H,dt,J=6.8Hz),4.20(1H,d,J=9.8 Hz),4.48(2H,s),6.61(1H,br),6.93(2H, d,J=9.0Hz),7.32-7.92(6H,m) FAB-MS(m/e):521[M+H]⁺

Example 1028

[0446] (R¹:H;R²:H;R³:i-Pr;R⁴:H;Z:Ph;R:4-N₃(CH₂)₃O-Ph)

[0447]¹HNMR(CDCl₃) δ:0.96(3H,d,J=6.6 Hz),1.14(3H,d,J=6.6Hz),1.60-1.69(1H,m),2.07-2.12(2H,m),3.54(2H,t,J=6.6 Hz),4.07(2H,t,J=6.2Hz),4.21(1H,d,J=9.9 Hz),6.92(2H,d,J=8.9 Hz),7.34-7.94(6H,m)FAB-MS(m/e):407[M+H]⁺

Example 1029

[0448] (R¹:H;R²:H;R³:i-Pr;R⁴:H;Z:Ph;R:4-t-BUO₂CCH(Me)O-Ph)

[0449]¹HNMR(CDCl₃) δ:0.91(3H,d,J=6.7 Hz),1.10(3H,d,J=6.7Hz),1.38-1.79(13H,m),4.19(1H,d,J=9.9 Hz),4.61-4.64(1H,m),6.86(2H,d,J=8.9Hz),7.31-7.34(1H,m),7.38(2H,d, J=8.9 Hz),7.57-7.62(2H,m),7.88-7.91(1H,m)FAB-MS(m/e):452[M+H]⁺

Example 1030

[0450] (R¹:H;R²:H;R³:i-Pr;R⁴:H;Z:Ph;R:4-n-PrNHCOCH(Me)O-Ph)

[0451]¹HNMR(CDCl₃) δ:0.78-0.89(3H,m),0.95(3H,d,J=6.8 Hz),1.11(3H,d,J=6.8Hz),1.40-1.74(6H,m),3.11-3.32(2H,m),4.20(1H,d,J=9.3Hz),4.64-4.70(1H,m),6.33-6.34(1H,m), 6.91(2H,d,J=8.2Hz),7.29-7.38(1H,m),7.39-7.43(2H,m),7.56-7.62(2H,m),7.87-7.92(1H,m)FAB-MS(m/e):437[M+H]⁺

Example 1031

[0452] (R¹:H;R^(2:)H;R³:i-Pr;R⁴:H;Z:Ph;R:4-F₃CSO₃-Ph)

[0453]¹HNMR(CDCl₃) δ:0.89(3H,d,J=6.7 Hz),1.12(3H,d,J=6.7Hz),1.59-1.67(1H,m),4.24(1H,d,J=9.6 Hz),7.31-7.34(1H,m),7.33(2H,d,J=8.9Hz),7.59-7.66(2H,m),7.61(2H,d, J=8.9 Hz),7.92-7.95(1H,m)FAB-MS(m/e):456[M+H]⁺

Example 1032

[0454] (R¹:H;R²:H;R³:i-Pr;R⁴:H;Z:Ph;R:4-t-BuO₂CCH═CH-Ph)

[0455]¹HNMR(CDCl₃) δ:0.91(3H,d,J=6.6 Hz),1.11(3H,d,J=6.6Hz),1.44(9H,s),1.50-1.66(1H,m),4.21(1H,d,J=9.7 Hz),6.38(1H,d,J=1 6.0Hz),7.32-7.36(1H,m),7.51-7.55(4H,m), 7.58-7.64(3H,m),7.90-7.94(1H,m)FAB-MS(m/e):434[M+H]⁺

Example 1033

[0456] (R¹:H;R²:H;R³:i-Pr;R⁴:H;Z:Ph;R:4-n-PrNHCOCH═CH-Ph)

[0457]¹HNMR(CDCl₃) δ:0.92(3H,d,J=6.7 Hz),0.97(3H,t,J=7.4Hz),1.11(3H,d,J=6.7 Hz),1.56-1.75(3H,m),3.36(2H,q,J=6.7Hz),4.22(1H,d,J=9.9 Hz),5.69(1H,s),6.41(1H,d,J=15.7 Hz),7.31-7.36(1H,m),7.47-7.54(4H,m),7.59-7.63(2H,m),7.61(1H,d,J=15.7Hz),7.90-7.95(1H,m) FAB-MS(m/e):419[M+H]⁺

Example 1034

[0458] (R¹:H;R²:H;R³:i-Pr;R⁴:H;Z:Ph;R:4-n-PrCH(Me)NHCOCH₂O-Ph)

[0459]¹HNMR(CDCl₃) δ:0.91 (3H,t,J=5.3 Hz),0.93(3H,d,J=6.6Hz),1.12(3H,d,J=6.6 Hz), 1.16(3H,d,J=6.6Hz),1.27-1.48(4H,m),1.61-1.69(1H,m),4.07-4.12(1H,m),4.22 (1H,d, J=9.8Hz),4.48(2H,s),6.26(1H,br),6.95(2H,d,J=8.9 Hz),7.32-7.94(6H,m)FAB-MS(m/e):451[M+H]⁺

Example 1035

[0460] (R¹:H;R²:;H;R³:i-Pr;R⁴:H;Z:Ph;R:4-EtCH(Me)NHCOCH₂O-Ph)

[0461]¹HNMR(CDCl₃) δ:0.87(3H,t,J=7.5 Hz),0.92(3H,d,J=6.6Hz),1.11(3H,d,J=6.7 Hz),1.15(3H,d,J=6.6Hz),1.46-1.52(2H,m),1.60-1.70(1H,m),3.98-4.03(1H,m),4.21(1H,d, J=9.8Hz),4.48(2H,s),6.24(1H,br),6.94(2H,d,J=8.9 Hz),7.31-7.93(6H,m)FAB-MS(m/e):437[M+H]⁺

Example 1036

[0462] (R¹:H;R²:H;R³:i-Pr;R⁴:H;Z:Ph;R:4-MeOCH₂O-Ph)

[0463]¹HNMR(CDCl₃) δ:0.97(3H,d,J=6.9 Hz),1.13(3H,d,J=6.9Hz),1.60-1.70(1H,m),3.49(3H,s),4.20(1H,d,J=9.6Hz),5.19(2H,s),7.05(2H,d,J=8.4 Hz),7.35-7.93(6H,m) ESI-MS(m/e):368[M+H]⁺

Example 1037

[0464] (R¹:H;R²:H;R³:i-Pr;R⁴:H;Z:Ph;R:4-EtCOCH₂O-Ph)

[0465]¹HNMR(CDCl₃) δ:0.93(3H,d,J=6.6 Hz),1.12(3H,d,J=6.6Hz),1.12(3H,t,J=7.3 Hz), 1.60-1.68(1H,m),2.26(2H,q,J7.3Hz),4.20(1H,d,J=9.9 Hz),4.58(2H,s),6.89(2H,d,J=8.9 Hz),7.32-7.92(6H,m)ESI-MS(m/e):394[M+H]⁺

Example 1038

[0466] (R¹:H;R²:H;R³:i-Pr;R⁴:H;Z:Ph;R:3-tBuO₂CCH₂O-Ph)

[0467]¹HNMR(CDCl₃) δ:0.94(3H,d,J=6.7 Hz),1.11(3H,d,J=6.7Hz),1.46(9H,s),1.61-1.73(1H,m),4.20(1H,d,J=9.9Hz),4.50(2H,s),6.89(1H,dd,J=2.3,8.1 Hz),7.02(1H,dd,J=1.1,2.3Hz),7.10(1H,dd,J=1.1,8.1 Hz),7.31(1H,t,J=8.1Hz),7.33-7.37(1H,m),7.56-7.61(2H,m), 7.87-7.92 (1H,m)FAB-MS(m/e):438[M+H]⁺

Example 1039

[0468] (R¹:H;R²:H;R³:i-Pr;R⁴:H;Z:Ph;R:3-HO₂CCH₂O-Ph)

[0469]¹HNMR(CDCl₃) δ:0.93(3H,d,J=6.6 Hz),1.10(3H,d,J=6.6Hz),1.59-1.69(1H,m),4.20(1H,d,J=9.0Hz),4.68(2H,s),6.90-6.94(1H,m),7.08-7.26(3H,m),7.31-7.36(1H,m),7.57-7.62(2H,m),7.88-7.93(1H,m) FAB-MS(m/e):382[M+H]⁺

Example 1040

[0470] (R¹:H;R^(2:)H;R³:i-Pr;R⁴:H-Z:Ph;R:3-n-PrNHCOCH₂O-Ph)

[0471]¹HNMR(CDCl₃) δ:0.93(3H,t,J=7.4 Hz),0.94(3H,d,J=6.6Hz),1.12(3H,d,J=6.6 Hz),1.52-1.72(3H,m),3.32(2H,q,J=6.8Hz),4.22(1H,d,J=9.8 Hz),4.47(2H,s),6.56-6.58(1H,m),6.91 (1H,dd,J=2.2,7.6Hz),7.11(1H,dd,J=1.1,2.2 Hz),7.14(1H,dd,J=1.1,7.8Hz),7.33-7.38(2H,m),7.58-7.64(2H,m),7.91-7.94(1H,m)FAB-MS(m/e):423[M+H]⁺

Example 1041

[0472] (R¹:H;R²:H;R³:i-Pr;R⁴:H;Z:Ph;R:4-H₂NC(Me)₂CH₂O₂CCH₂O-PhFAB-MS(m/e):453[M+H]⁺

Example 1042

[0473] (R¹:H;R²:H;R³:i-Pr;R⁴:H;Z:Ph;R:4-morpholinoCOCH₂O-Ph)

[0474]¹HNMR(CDCl₃) δ:0.94(3H,d,J=6.7 Hz),1.13(3H,d,J=6.7Hz),1.60-1.68(1H,m),3.59-3.69(8H,m),4.21(1H,d,J=9.8Hz),4.72(2H,s),6.96(2H,d,J=9.0 Hz),7.33-7.93(6H,m) ESI-MS(m/e):451[M+H]⁺

Example 1043

[0475] (R¹:H;R²:H;R³:i-Pr;R⁴:H;Z:Ph;R:4-(4-Cl-Ph)-COCH₂O-Ph)

[0476]¹HNMR(CDCl₃) δ:0.93(3H,d,J=6.6Hz),1.11(3H,d,J=6.6Hz),1.62-1.66(1H,m),4.19(1H,d,J=9.9 Hz),5.25(2H,s),6.93(2H,d,J=8.9Hz),7.32-7.97(10H,m) ESI-MS(m/e):476[M+H]⁺

Example 1044

[0477] (R¹:H;R²:H;R³:i-Pr;R⁴:H;Z:Ph;R:4-PhCOCH₂O-Ph)

[0478]¹HNMR(CDCl₃) δ:0.93(3H,d,J=6.7 Hz),1.11(3H,d,J=6.7Hz),1.61-1.70(1H,m),4.19(1H,d, J=9.9 Hz),5.31 (2H,s),6.94(2H,d,J=9.0Hz),7.33-8.01(11H,m) ESI-MS(m/e):442[M+H]⁺

Example 1045

[0479] (R¹:H;R²:H;R³:i-Pr;R⁴:H;Z:Ph;R:4-(4-pyridyl)-CH₂NHCOCH₂O-Ph)

[0480]¹HNMR(CDCl₃) δ:0.92(3H,d,J=6.5 Hz),1.12(3H,d,J=6.5Hz),1.61-1.67(1H,m),4.21(1H,d,J=9.7 Hz),4.57(1H,d,J=6.4Hz),4.60(2H,s),6.96(2H,d,J=8.9 Hz),7.20-8.57(1-H,m)ESI-MS(m/e):472[M+H]⁺

Example 1046

[0481] (R¹:H;R²:H;R³:i-Pr;R⁴:H;Z:Ph;R:4-H₂NCH₂CH₂NHCOCH₂O-Ph)

[0482]¹HNMR(methanol-d₄)δ:0.87-1.09(6H,m),1.57-2.15(1H,m),3.06-3.12(2H,m),3.52-3.59(2H,m),4.20(1H,d,J=9.5Hz),4.54-4.64(2H,m),6.90-7.91(8H,m) FAB-MS(m/e):424[M+H]⁺

Example 1047

[0483] (R¹:H;R²:H;R³:i-Pr;R⁴:H;Z:Ph;R:4-Cl-3-NO₂-Ph)

[0484] ESI-MS(m/e):387[M+H]⁺

Example 1048

[0485] (R¹:H;R²:H;R³:i-Pr;R⁴:H;Z:Ph;R:4-Cl-3-F-Ph)

[0486]¹HNMR(CDCl₃) δ:0.94(3H,d,J=6.6 Hz),1.13(3H,d,J=6.6Hz),1.59-1.72(1H,m),4.22(1H,d,J=9.4 Hz),7.24-7.36(3H,m),7.44(1H,t,J=7.7Hz),7.59-7.65(2H,m),7.90-7.94(1H,m) FAB-MS(m/e):360[M+H]⁺

Example 1049

[0487] (R¹:H;R²:H;R¹:i-Pr;R⁴:H;Z:Ph;R:4-Cl-3-Me-Ph)

[0488]¹HNMR(CDCl₃) δ:0.94(3H,d,J=6.7 Hz),1.12(3H,d,J=6.7Hz),1.58-1.72(1H,m),2.38(3H, s),4.20(1H,d,J=9.9Hz),7.21-7.27(1H,m),7.31-7.35(1H,m),7.35(2H,d,J=8.5 Hz), 7.57-7.63(2H,m),7.88-7.95(1H,m) FAB-MS(m/e):356[M+H]⁺

Example 1050

[0489] (R¹:H;R²:H;R³:i-Pr;R⁴:H;Z:Ph;R:3-NH₂-4-Cl-Ph)

[0490]¹HNMR(CDCl₃) δ:0.96(3H,d,J=6.6Hz),1.13(3H,d,J=6.5Hz),1.60-1.77(1H,m),4.19(1H,d,J=9.9Hz),6.75(1H,dd,J=2.4,8.2Hz),6.92(1H,d,J=2.4,Hz),7.23(1H,d,J=8.2,Hz),7.33-7.39(1H,m),7.57-7.63(2H,m),7.86-7.93(1H,m) FAB-MS(m/e):357[M+H]⁺

Example 1051

[0491] (R¹:H;R²:H;R³:i-Pr;R⁴:H;Z:Ph;R:3-Cl-4-MeO-Ph)

[0492]¹HNMR(CDCl₃) δ:0.95(3H,d,J=6.7 Hz),1.13(3H,d,J=6.7Hz)1.57-1.65(1H,m),3.91(3H, s),4.20(1H,d,J=9.9 Hz),6.92(1H,d,J=8.6Hz),7.33-7.93(6H,m) FAB-MS(m/e):372[M+H]⁺

Example 1052

[0493] (R¹:H;R²:H;R³:i-Pr;R⁴:H;Z:Ph;R:3-Cl-4-Me-Ph)

[0494]¹HNMR(CDCl₃) δ:0.95(3H,d,J=6.7 Hz),1.12(3H,d,J=6.7Hz),1.62-1.69(1H,m),3.27(3H, s),4.20(1H,d,J=9.8Hz),7.26-7.33(2H,m),7.33-7.36(1H,m),7.49(1H,s),7.57-7.62(2H,m),7.89-7.93(1H,m)FAB-MS(m/e):356[M+H]⁺

Example 1053

[0495] (R¹:H;R²:H;R³:i-Pr;R⁴:H;Z:Ph;R:4-Br-3-Cl-Ph)

[0496]¹HNMR(CDCl₃) δ:0.88(3H,d,J=6.7 Hz),1.12(3H,d,J=6.7Hz),1.50-1.60(1H,m),4.24(1H,d, J=9.6 Hz),7.50-7.95(7H,m)FAB-MS(m/e):420/422[M+H]⁺

Example 1054

[0497] (R¹:H;R²:H;R³:i-Pr;R⁴:H;Z:Ph;R:4-Br-2-Cl-Ph)

[0498]¹HNMR(CDCl₃) δ:0.94(3H,d,J=6.6 Hz),1.13(3H,d,J=6.5Hz),1.62-1.67(1H,m),4.22(1H,d, J=9.7 Hz),7.22-7.94(7H,m)FAB-MS(m/e):420/422[M+H]⁺

Example 1055

[0499] (R¹:H;R²:H;R³:i-Pr;R⁴:H;Z:Ph;R:4-F-3-Me-Ph)

[0500]¹HNMR(CDCl₃) δ:0.93(3H,d,J=6.7 Hz),1.12(3H,d,J=6.7Hz),1.61-1.68(1H,m),2.28 (3H,s),4.20(1H,d,J=9.9 Hz),7.01(1H,t,J=8.9Hz),7.27-7.35(3H,m),7.59-7.62(2H,m), 7.90-7.93(1H,m)FAB-MS(m/e):340[M+H]⁺

Example 1056

[0501] (R¹:H,R²:H;R³:i-Pr;R⁴:H;Z:Ph;R:3-F-4-Me-Ph)

[0502]¹HNMR(CDCl₃) δ:0.94(3H,d,J=6.7 Hz),1.12(3H,d,J=6.7Hz),1.63-1.70(1H,m),2.28(3H,s),4.21(1H,d,J=9.9 Hz),7.16(1H,d,J=7.2Hz),7.18(1H,s),7.20(1H,d,J=7.2 Hz), 7.33-7.36(1H,m),7.57-7.63(2H,m),7.90-7.93(1H,m) FAB-MS(m/e):340[M+H]⁺

Example 1057

[0503] (R¹:H;R²:H;R³:i-Pr;R⁴:H;Z:Ph;R:3-Br-4-HO-Ph)

[0504]¹HNMR(CDCl₃) δ:0.95(3H,d,J=6.6 Hz),1.13(3H,d,J=6.6Hz),1.62-1.72(1H,m),4.20(1H,d,J=9.9 Hz),5.70(1H,s),7.02(1H,d,J=8.6Hz),7.30-7.37(1H,m),7.32(1H,d,J=8.6 Hz), 7.58-7.65(2H,m),7.64(1H,s),7.90-7.93(1H,m) FAB-MS(m/e):402/404[M+H]⁺

Example 1058

[0505] (R¹:H;R¹:H;R³:i-Pr;R⁴:H;Z:Ph;R:3-Br-4-MeO-Ph)

[0506]¹HNMR(CDCl₃) δ:0.95(3H,d,J=6.7 Hz),1.13(3H,d,J=6.7Hz),1.61-1.73(1H,m),3.91(3H, s),4.20(1H,d,J=9.9 Hz),6.90(1H,d,J=8.6Hz),7.32-7.38(1H,m),7.42(1H,dd,J=2.3,8.6 Hz),7.58-7.64(2H,m),7.66(1H,d,J=2.3 Hz),7.88-7.94(1H,m)FAB-MS(m/e):416/418[M+H]⁺

Example 1059

[0507] (R¹:H;R²:H;R³:i-Pr;R⁴:H;Z:Ph;R:3-Br-4-F-Ph)

[0508] ESI-MS(m/e):404[M+H]⁺

Example 1060

[0509] (R¹:H;R²:H;R³:i-Pr;R⁴:H;Z:Ph;R:3-F-4-Ph-Ph)

[0510]¹HNMR(CDCl₃) δ:0.88(3H,d,J=6.5 Hz),1.15(3H,d,J=6.5Hz),1.65-1.80(1H,m),4.23(1H,d, J=9.9Hz),7.28-7.56(9H,m),7.56-7.66(2H,m),7.91-7.95(1H,m)FAB-MS(m/e):402[M+H]⁺

Example 1061

[0511] (R¹:H;R²:H;R³:i-Pr;R⁴:H;Z:Ph;R:4-HO-3-I-Ph)

[0512]¹HNMR(CDCl₃) δ:0.95(3H,d,J=6.6 Hz),1.13(3H,d,J=6.6Hz),1.63-1.69(1H,m),4.19(1H,d, J=9.9 Hz),5.71(1H,s),6.98(1 H,d,J=8.5Hz),7.32-7.93(6H,m) FAB-MS(m/e):450[M+H]⁺

Example 1062

[0513] (R¹:H;R²:H;R³:i-Pr;R⁴:H;Z:Ph;R:5-HO-2-I-Ph)

[0514]¹HNMR(CDCl₃) δ:0.95(3H,d,J=6.7 Hz),1.12(3H,d,J=6.7Hz),1.63-1.75(1H,m),4.20(1H,d,J=9.9Hz),6.04(1H,brs),6.82(1H,dd,J=2.1,8.2 Hz),7.11(1H,d,J=2.1Hz),7.33-7.36(1H,m),7.55-7.62(2H,m),7.69(1H,d,J=8.2 Hz),7.84-7.87(1H,m)FAB-MS(m/e):450[M+H]⁺

Example 1063

[0515] (R¹:H;R²:H;R³:i-Pr;R⁴:H;Z:Ph;R:3-I-4-MeO-Ph)

[0516]¹HNMR(CDCl₃) δ:0.96(3H,d,J=6.6 Hz),1.13(3H,d,J=6.6Hz),1.59-1.68(1H,m),3.89(3H,s),4.20(1H,d,J=9.9 Hz),6.81(1H,d,J=8.6Hz),7.34-7.93(6H,m) FAB-MS(m/e):464[M+H]⁺

Example 1064

[0517] (R¹:H;R²:H;R³:i-Pr;R⁴:H;Z:Ph;R:2-I-5-MeO-Ph)

[0518]¹HNMR(CDCl₃) δ:0.98(3H,d,J=6.6 Hz),1.13(3H,d,J=6.6Hz),1.63-1.71(1H,m), 3.86(3H,s),4.22(1H,d,J=10.1Hz),6.87(1H,dd,J=1.9,8.0Hz),6.91(1H,d,J=1.9Hz),7.35-7.37(1H,m),7.58-7.64(2H,m),7.79(1H,d,J=8.0Hz),7.92(1H,dd,J=3.0,5.7 Hz) FAB-MS(m/e):464[M+H]⁺

Example 1065

[0519] (R¹:H;R²:H;R³:i-Pr;R⁴:H;Z:Ph;R:4-MeO-3-Me-Ph)

[0520]¹HNMR(CDCl₃) δ:0.95(3H,d,J=6.6 Hz),1.11(3H,d,J=6.6Hz),1.60-1.70(1H,m),2.18(3H,s),3.83(3H,s),4.18(1H,d,J=10.0Hz),6.80(1H,d,J=8.6 Hz),7.20(1H,d,J=2.6 Hz),7.30(1H,dd,J=2.6,8.6Hz),7.32-7.36(1H,m),7.54-7.61 (2H,m),7.88-7.92(1H,m)FAB-MS(m/e):352[M+H]⁺

Example 1066

[0521] (R¹:H;R²:H;R³:i-Pr;R⁴:H;Z:Ph;R:4-HO(CH₂)₃O-3-I-Ph)

[0522]¹HNMR(CDCl₃) δ:0.97(3H,d,J=6.7 Hz),1.14(3H,d,J=6.7Hz),1.57-1.70(1H,m),2.13(2H, dt,J=5.6 Hz),3.95(2H,t,J=5.6Hz),4.20(2H,t,J=5.6 Hz),4.21(1H,d,J=9.9 Hz),6.83(1H,d,J=8.6Hz),7.35-7.94(6H,m) FAB-MS(m/e):508[M+H]⁺

Example 1067

[0523] (R¹:H;R²:H;R³:i-Pr;R⁴:H;Z:Ph;R:4-HO(CH₂)₂O-3-I-Ph)

[0524]¹HNMR(CDCl₃) δ:0.96(3H,d,J=6.7 Hz),1.15(3H,d,J=6.7Hz),1.58-1.68(1H,m),4.01(2H,t,J=4.4 Hz),4.15(2H,t,J=4.4Hz),4.21(1H,d,J=9.9 Hz),6.83(1H,d,J=8.6 Hz), 7.34-7.94(6H,m)FAB-MS(m/e):494[M+H]⁺

Example 1068

[0525] (R¹:H;R²:H;R³:i-Pr;R⁴:H;Z:Ph;R:4-HOC(Me)₂(CH₂)₂O-3-I-Ph)

[0526]¹HNMR(CDCl₃) δ:0.96(3H,d,J=6.6 Hz),1.13(3H,d,J=6.6Hz),1.34(6H,s),1.60-1.65(1H, m),2.08(2H,t,J=6.0 Hz),4.19(1H,d,J=9.9Hz),4.23(2H,t,J=6.0 Hz),6.82(1H,d,J=8.7 Hz), 7.32-7.94(6H,m)FAB-MS(m/e):536[M+H]⁺

Example 1069

[0527] (R¹:H;R²:H;R³:i-Pr;R⁴:H;Z:Ph;R:4-t-BUO₂C(CH₂)₄O-3-I-Ph)

[0528]¹HNMR(CDCl₃) δ:0.95(3H,d,J=6.6 Hz),1.12(3H,d,J=6.6Hz),1.44(9H,s),1.60-1.67(1H,m),1.82-1.86(4H,m),2.32(2H,t,J=6.88Hz),4.01(2H,t,J=5.3 Hz),4.18(1H,d,J=10.0 Hz), 6.75(1H,d,J=8.6Hz),7.32-7.91(6H,m) FAB-MS(m/e):606[M+H]⁺

Example 1070

[0529] (R¹:H;R²:H;R³:i-Pr;R⁴:H;Z:Ph;R:3-I-4-PhCH₂O-Ph)

[0530]¹HNMR(CDCl₃) δ:0.96(3H,d,J=6.7 Hz),1.13(3H,d,J=6.7Hz),1.60-1.75(1H,m),4.20(1H,d, J=9.9 Hz),5.16(2H,s),6.86(1H,d,J=8.6Hz),7.34-7.93(11H,m) FAB-MS(m/e):540[M+H]⁺

Example 1071

[0531] (R¹:H;R²:H;R³:i-Pr;R⁴:H;Z:Ph;R:4-H₂NCOCH₂O-3-I-Ph)

[0532]¹HNMR(CDCl₃) δ:0.95(3H,d,J=6.7 Hz),1.13(3H,d,J=6.7Hz),1.61-1.69(1H,m), 4.21(1H,d,J=9.9Hz),4.53(2H,s),5.86(1H,br),6.78(1H,8,J=8.6Hz),6.86(1H,br),7.33-7.94(6H,m) FAB-MS(m/e):507[M+H]⁺

Example 1072

[0533] (R¹:H;R²:H;R³:i-Pr;R⁴:H;Z:Ph;R:3-I-4-MeNHCOCH₂O-Ph)

[0534]¹HNMR(CDCl₃) δ:0.95(3H,d,J=6.6 Hz),1.13(3H,d,J=6.6Hz),1.61-1.69(1H,m),2.97(3H, d, J=5.0 Hz),4.21(1H,d,J=9.8Hz),4.53(2H,s),6.77(1H,d,J=8.6 Hz),6.87(1H,br),7.33-7.94(6H,m)FAB-MS(m/e):521[M+H]⁺

Example 1073

[0535] (R¹:H;R^(2:)H;R³:i-Pr;R⁴:H;Z:Ph;R:4-EtNHCOCH₂O-3-I-Ph)

[0536]¹HNMR(CDCl₃) δ:0.95(3H,d,J=6.6 Hz),1.13(3H,d,J=6.6Hz),1.24(3H,t,J=7.3 Hz),1.61-1.69(1H,m),3.44(2H,dt,J=7.3Hz),4.21(1H,d,J=9.8 Hz),4.51 (2H,s),6.77(1H,d,J=8.6 Hz),6.89(1H,br),7.33-7.94(6H,m) FAB-MS(m/e):535[M+H]⁺

Example 1074

[0537] (R¹:H;R²:H;R³:i-Pr;R⁴:H;Z:Ph;R:3-I-4-n-PrNHCOCH₂O-Ph)

[0538]¹HNMR(CDCl₃) δ:0.97(3H,t,J=7.8 Hz),1.00(3H,d,J=6.7Hz),1.13(3H,d,J=6.7 Hz), 1.57-1.69(3H,m),3.37(2H,dt,J=7.0Hz),4.22(1H,d,J=9.8 Hz),4.52(2H,s),6.78(1H,d,J=8.6 Hz),6.91(1H,br),7.33-7.94(6H,m) FAB-MS(m/e):549[M+H]⁺

Example 1075

[0539] (R¹:H;R²:H;R³:i-Pr;R⁴:H;Z:Ph;R:3-I-4-i-PrNHCOCH₂O-Ph)

[0540]¹HNMR(CDCl₃) δ:0.95(3H,d,J=6.6 Hz),1.13(3H,d,J=6.6Hz),1.25(6H,d,J=6.3 Hz),1.61-1.69(1H,m),4.11-4.20(1H,m),4.21(1H,d,J=9.8Hz),4.49(2H,s),6.77(1H,br),6.77(1H,d, J=9.8 Hz),7.33-7.94(6H,m)FAB-MS(m/e):549[M+H]⁺

Example 1076

[0541] (R¹:H;R²:H;R³:i-Pr;R⁴:H;Z:Ph;R:4-n-BuNHCOCH₂O-3-I-Ph)

[0542]¹HNMR(CDCl₃) δ:0.92-0.97(6H,m),1.12(3H,d,J=6.8Hz),1.35-1.68(5H,m),3.39(2H,dt J=6.3 Hz),4.20(1H,d,J=9.9 Hz),4.51(2H,s),6.76(1H,d,J=8.6 Hz),6.90(1H,br),7.32-7.93(6H, m)FAB-MS(m/e):563[M+H]⁺

Example 1077

[0543] (R¹:H;R²:H;R³:i-Pr;R⁴:H;Z:Ph;R:4-t-BuNHCOCH₂O-3-I-Ph)

[0544]¹HNMR(CDCl₃) δ:0.94(3H,d,J=6.7 Hz),1.13(3H,d,J=6.7Hz),1.44(9H,s),1.61-1.69(1H, m),4.21(1H,d,J=9.8Hz),4.40(2H,s),6.76(1H,d,J=8.6 Hz),6.86(1H,br),7.33-7.94(6H,m)FAB-MS(m/e):563[M+H]⁺

Example 1078

[0545] (R¹:H;R²:H;R³:i-Pr;R⁴:H;Z:Ph;R:4-i-BuNHCOCH₂O-Ph)

[0546]¹HNMR(CDCl₃) δ:0.88-0.96(9H,m),1.11(3H,d,J=6.7Hz),1.60-1.83(2H,m),3.18(2H,t, J=6.5 Hz),4.20(1H,d,J=9.8 Hz),4.51(2H,s),6.54(1H,br),6.95(2H,d,J=8.9 Hz),7.31-7.93(6H, m)FAB-MS(m/e):437[M+H]⁺

Example 1079

[0547] (R¹:H;R²:H;R³:i-Pr;R⁴:H;Z:Ph;R:4-t-BuO₂CCH₂O-3-I-Ph)

[0548]¹HNMR(CDCl₃) δ:0.96(3H,d,J=6.6 Hz),1.13(3H,d,J=6.6Hz),1.48(9H,s),1.51-1.68(1H,m),4.20(1H,d,J=9.9 Hz),4.61(2H,s),6.69(1H,d,J=8.6 Hz),7.34-7.94(6H,m) FAB-MS(m/e):564[M+H]⁺

Example 1080

[0549] (R¹:H;R²:H;R³:i-Pr;R⁴:H;Z:Ph;R:3-I-4-PhCH₂NHCOCH₂O-Ph)

[0550]¹HNMR(CDCl₃) δ:0.94(3H,d,J=6.7 Hz),1.13(3H,d,J=6.7Hz),1.63-1.66(1H,m),4.20(1H,d,J=9.8 Hz),4.58(2H,s),4.59(2H,d,J=5.5Hz),6.79(1H,d,J=8.6Hz),7.27-7.94(11H,m) FAB-MS(m/e):597[M+H]⁺

Example 1081

[0551](R¹:H;R²:H;R³:i-Pr;R⁴:H;Z:Ph;R:3-I-4-(2-tetrahydrofuryl)-CH₂NHCOCH₂O-Ph)

[0552]¹HNMR(CDCl₃) δ:0.96(3H,d,J=6.6 Hz),1.14(3H,d,J=6.6Hz),1.56-2.06(5H,m), 3.38-4.14(5H,m),4.22(1H,d,J=9.8Hz),4.54(2H,s),6.78(1H,d,J=8.6 Hz),7.23(1H,br),7.33-7.96(6H,m)ESI-MS(m/e):591[M+H]⁺

Example 1082

[0553] (R¹:H;R²:H;R³:i-Pr;R⁴:H;Z:Ph;R:4-cycloPrNHCOCH₂O-3-I-Ph)

[0554]¹HNMR(CDCl₃) δ:0.61-0.64(2H,m),0.85-0.89(2H,m),0.95(3H,d,J=6.7Hz),1.14(3H,d, J=6.7 Hz),1.62-1.67(1H,m),2.84-2.88(1H,m),4.22(1H,d,J=9.9Hz),4.51 (2H,s),6.76(1H,d, J=8.6 Hz),7.00(1H,br),7.33-7.95(6H,m)FAB-MS(m/e):547[M+H]⁺

Example 1083

[0555] (R¹:H;R^(2:)H;R³:i-Pr;R⁴:H;Z:Ph;R:4-cycloPentylNHCOCH₂O-3-I-Ph)

[0556]¹HNMR(CDCl₃) δ:0.95(3H,d,J=6.6 Hz),1.13(3H,d,J=6.6Hz),1.50-1.77(7H,m),2.00-2.03(2H,m),4.22(1H,d,J=9.6Hz),4.24-4.36(1H,m),4.50(2H,s),6.77(1H,d,J=8.6Hz),6.95(1H,br),7.33-7.94(6H,m) FAB-MS(m/e):575[M+H]⁺

Example 1084

[0557] (R¹:H;R²:H;R³:i-Pr;R⁴:H;Z:Ph;R:4-cycloHexylNHCOCH₂O-3-I-P).

[0558]¹HNMR(CDCl₃) δ:0.94(3H,d,J=6.7 Hz),1.12(3H,d,J=6.7Hz),1.26-1.97(11H,m),3.89-3.93(1H,m),4.21(1H,d,J=9.7Hz),4.99(2H,s),6.77(1H,d,J=8.6 Hz),6.89(1H,brd, J=10.0Hz),7.33-7.93(6H,m) FAB-MS(m/e):589[M+H]⁺

Example 1085

[0559] (R¹:H;R²:H;R³:i-Pr;R⁴:H;Z:Ph;R:4-cycloPrNHCOCH₂O-3-F-Ph)

[0560]¹HNMR(CDCl₃) δ:0.57-0.59(2H,m),0.83-0.88(2H,m),0.93(3H,d,J=6.6Hz),1.13(3H,d, J=6.6 Hz),1.60-1.68(1H,m),2.75-2.83(1H,m),4.21(1H,d,J=9.7Hz),4.51(2H,s),6.68(1H,br),6.92-7.93(7H,m) ESI-MS(m/e):439[M+H]⁺

Example 1086

[0561] (R¹:H;R²:H;R³:i-Pr;R⁴:H;Z:Ph;R:4-Me(CH2)₉NHCOCH2O-3-I-Ph)

[0562]¹HNMR(CDCl₃) δ:0.88(3H,t,J=6.3 Hz),0.95(3H,d,J=6.6Hz),1.13(3H,d,J=6.6 Hz),1.20-1.40(14H,m),1.56-1.70(3H,m),3.38(2H,dt,J=6.6 Hz),4.20(1H,d,J=9.9Hz),4.51(2H,s), 6.77(1H,d,J=8.6 Hz),6.92(1H,br),7.33-7.94(6H,m)FAB-MS(m/e):647[M+H]⁺

Example 1087

[0563] (R¹:H;R²:H;R³:i-Pr;R⁴:H;Z:Ph;R:4-HO₂CCH₂O-3-I-Ph)

[0564]¹HNMR(CDCl₃) δ:0.96(3H,d,J=6.6 Hz),1.13(3H,d,J=6.6Hz),1.51-1.68(1H,m),4.20(1H,d, J=9.9 Hz),4.61 (2H,s),6.69(1H,d,J=8.6Hz),7.34-7.94(6H,m) FAB-MS(m/e):508[M+H]⁺

Example 1088

[0565] (R¹:H;R²:H;R³:i-Pr;R¹:H;Z:Ph;R:4-N₃(CH₂)₃O-3-I-Ph)

[0566]¹HNMR(CDCl₃) δ:0.97(3H,d,J=6.6 Hz),1.13(3H,d,J=6.6Hz),1.60-1.68(1H,m),2.09-2.13(2H,m),3.63(2H,t,J=6.5 Hz),4.11 (2H,t,J=5.3Hz),4.20(1H,d,J=9.9 Hz),6.79(1H,d,J=8.6 Hz),7.34-7.94(6H,m)FAB-MS(m/e):533[M+H]⁺

Example 1089

[0567] (R¹:H;R¹:H;R³:i-Pr;R⁴:H;Z:Ph;R:3-I-4-n-PrNHCO(CH₂)₄O-Ph)

[0568]¹HNMR(CDCl₃) δ:0.92(3H,t,J=7.4 Hz),0.96(3H,d,J=6.7Hz),1.13(3H,d,J=6.7Hz),1.45-1.55(2H,m),1.62-1.69(1H,m),1.87-1.92(4H,m),2.28-2.32(2H,m),3.21(2H,dt,J=7.0Hz), 4.02-4.09(2H,br),4.20(1H,d,J=9.9 Hz),5.51(1H,br),6.77(1H,d,J=8.6Hz), 7.34-7.93(6H,m) FAB-MS(m/e):591[M+H]⁺

Example 1090

[0569] (R¹:H;R²:H;R³:i-Pr;R⁴:H;Z:Ph;R:4-Et₂NCOCH₂O-3-I-Ph)

[0570]¹HNMR(CDCl₃) δ:0.95(3H,d,J=6.6 Hz),1.12(6H,m),1.22(3H,t,J=7.0Hz),1.60-1.68(1H, m),3.39-3.45(4H,m),4.19(1H,d,J=9.9Hz),4.77(2H,s),6.88(1H,d,J=8.7 Hz),7.34-7.93(6H, m)FAB-MS(m/e):563[M+H]⁺

Example 1091

[0571] (R¹:H;R²:H;R³:i-Pr;R⁴:H;Z:Ph;R:3-I-4-n-PrN(Me)COCH₂O-Ph)

[0572]¹HNMR(CDCl₃) δ:0.84(3H,t,J=7.3 Hz),0.98(3H,d,J=6.7Hz),1.15(3H,d,J=6.7Hz),1.50-1.69(3H,m),2.96(3H,s,rotomer),3.11(3H,s,rotomer),3.37(2H,t,J=7.3Hz),4.80(1H,d,J=10.0 Hz),4.79(2H,s,rotomer),4.81(2H,s,rotomer),6.87-7.94(7H,m,rotomer) FAB-MS(m/e):563[M+H]⁺

Example 1092

[0573] (R¹:H;R²:H;R³:i-Pr;R⁴:H;Z:Ph;R:3-Cl-4-n-PrNHCOCH₂O-Ph)

[0574]¹HNMR(CDCl₃) δ:0.93-0.98(6H,m),1.13(3H,d,J=6.6Hz),1.56-1.70(3H,m),3.34(2H,dt, J=6.6 Hz),4.21(1H,d,J=9.8Hz),4.54(2H,s),6.80(1H,br),6.92(1H,d,J=8.6 Hz),7.33-7.94(6H, m)ESI-MS(m/e):457[M+H]⁺

Example 1093

[0575] (R¹:H;R²:H;R³:i-Pr;R⁴:H;Z:Ph;R:3-Br-4-n-PrNHCOCH₂O-Ph)

[0576]¹HNMR(CDCl₃) δ:0.97(3H,t,J=7.8 Hz),0.97(3H,d,J=6.6Hz),1.13(3H,d,J=6.6 Hz),1.56-1.69(3H,m),3.34(2H,q,J=6.6Hz),4.22(1H,d,J=10.0 Hz),4.53(2H,s),6.87-6.89(1H,m), 6.87(1H,d,J=8.5Hz),7.34-7.36(1H,m),7.45(1H,d,J=8.5 Hz),7.60-7.63(2H,m),7.72(1H,s),7.89-7.94(1H,m) FAB-MS(m/e):50 1/503[M+H]⁺

Example 1094

[0577] (R¹:H;R²:H;R³:i-Pr;R⁴:H;Z:Ph;R:3-F-4-n-PrNHCOCH₂O-Ph)

[0578]¹HNMR(CDCl₃) δ:0.90-0.95(6H,m),1.12(3H,d,J=6.6Hz),1.54-1.70(3H,m),3.32(2H,dt J=6.6 Hz),4.21 (1H,d,J=9.7Hz),4.53(2H,s),6.65(1H,br),6.94-7.93(7H,m) FAB-MS(m/e):441[M+H]⁺

Example 1095

[0579] (R¹:H;R²:H;R³:i-Pr;R⁴:H;Z:Ph;R:3-Me-4-n-PrNHCOCH₂O-Ph)

[0580]¹HNMR(CDCl₃) δ:0.92(3H,t,J=7.6 Hz),0.95(3H,d,J=6.8Hz),1.11(3H,d,J=6.8 Hz),1.53-1.74(3H,m),2.28(3H,s),3.33(2H,q,J=6.6Hz),4.21(1H,d,J=9.9 Hz),4.49(2H,s),6.51-6.52 (1H, m),6.78(1H,d,J=8.2Hz),7.29-7.36(3H,m),7.56-7.62(2H,m),7.88-7.92(1H,m)FAB-MS(m/e):437[M+H]⁺

Example 1096

[0581] (R¹:H;R²:H;R³:i-Pr;R⁴:H;Z:Ph;R:4-EtNHCOCH₂O-3-F-Ph)

[0582]¹HNMR(CDCl₃) δ:0.94(3H,d,J=6.6 Hz),1.13(3H,d,J=6.6Hz),1.20(3H,t,J=7.3 Hz),1.60-1.68(1H,m),3.41 (2H,dt,J=7.3Hz),4.21(1H,d,J=9.8 Hz),4.53(2H,s),6.63(1H,br),6.95-7.94 (7H,m)ESI-MS(m/e):427[M+H]⁺

Example 1097

[0583] (R¹:H;R²:H;R³:i-Pr;R⁴:H;Z:Ph;R:3-I-4-i-PrNHCOC(Me)₂CH₂O-Ph)

[0584]¹HNMR(CDCl₃) δ:0.91 (3H,t,J=7.4 Hz),0.96(3H,d,J=6.7Hz),1.13(3H,d,J=6.7 Hz),1.52-1.69(3H,m),3.23(2H,dt,J=5.7Hz),3.93-3.99(2H,m),4.19(1H,d,J=11.0 Hz), 6,27(1H,br), 6.77(1Hd,J=8.7Hz),7.32-7.92(6H,m) FAB-MS(m/e):427[M+H]⁺

Example 1098

[0585] (R¹:H;R²:H;R³:i-Pr;R⁴:H-Z:Ph;R:3-Br-4-CH₂═CHCH₂NHCOCH₂O-Ph)

[0586]¹HNMR(CDCl₃) δ:0.94(3H,t,J=6.6 Hz),1.13(3H,d,J=6.6Hz),1.60-1.70(1H,m),4.00-4.04(2H,m),4.22(1H,d,J=9.7Hz),4.56(2H,s),5.18(1H,d,J=10.3 Hz),5.24(1H,d,J=19.7Hz),5.81-5.96(1H,m),6.88-6.92(1H,m),6.89(1H,d,J=8.6Hz),7.33-7.37(1H,m),7.45(1H,dd, J=2.3, 8.6Hz),7.61-7.65(2H,m),7.72(1H,d,J=2.3 Hz),7.90-7.95(1H,m)FAB-MS(m/e):499/501[M+H]⁺

Example 1099

[0587] (R¹:H;R²:H;R³:i-Pr;R⁴:H;Z:Ph;R:4-i-BuNHCOCH₂O-3-F-Ph)

[0588]¹HNMR(CDCl₃) δ:0.90(6H,d,J=6.7 Hz),0.93(3H,d,J=6.7Hz),1.12(3H,d,J=6.7 Hz),1.59-1.69(1H,m),1.77-1.84(1H,m),3.18(2H,t,J=6.7Hz),4.20(1H,d,J=9.7 Hz),4.54(2H,s),6.68(1H,br),6.94-7.93(7H,m)ESI-MS(m/e):455[M+H]⁺

Example 1100

[0589] (R¹:H;R²:H;R³:i-Pr;R⁴:H;Z:Ph;R:3-t-BuO₂CCH═CH-4-n-PrNHCOCH₂OPh)

[0590]¹HNMR(CDCl₃) δ:0.88(3H,t,J=7.1 Hz),0.92(3H,d,J=6.5Hz),1.12(3H,d,J=6.5 Hz),1.41-1.68(3H,m),1.54(9H,s),3.31 (2H,q,J=6.7Hz),4.22(1H,d,J=9.4 Hz),4.57(2H,s),6.39-6.44(1H,m),6.41(1H,d,J=16.2Hz),6.89(1H,d,J=8.5 Hz),7.32-7.34(1H,m),7.45(1H,dd,J=2.3, 8.5Hz),7.58-7.64(2H,m),7.67(1H,d,J=2.3 Hz),7.86(1H,d,J=16.2Hz),7.93-7.94(1H,m) FAB-MS(m/e):549[M+H]⁺

Example 1101

[0591] (R¹:H;R²:H;R³:i-Pr;R⁴:H;Z:Ph;R:3-HO₂CCH═CH-4-n-PrNHCOCH₂O-Ph)

[0592]¹HNMR(CDCl₃) δ:0.91(3H,t,J=7.4 Hz),0.93(3H,d,J=6.6Hz),1.12(3H,d,J=6.6 Hz),.153-1.64(3H,m),3.32(2H,q,J=6.7Hz),4.23(1H,d,J=9.8 Hz),4.59(2H,s),6.46-6.48(1H,m),6.51(1H,d,J=16.1Hz),6.92(1H,d,J=8.7 Hz),7.32-7.35(1H,m),7.50(1H,dd,J=2.3,87Hz),7.59-7.63(2H,m),7.70(1H,d,J=2.3 Hz),7.92-7.95(1H,m),8.01(1H,d,J=16.1Hz) FAB-MS(m/e):493[M+H]⁺

Example 1102

[0593] (R¹:H;R²:H;R³:i-Pr;R⁴:H;Z:Ph;R:3-I-4-MeOCH₂CH₂NHCOCH₂O-Ph)

[0594]¹HNMR(CDCl₃) δ:0.95(3H,d,J=6.7 Hz),1.13(3H,d,J=6.7Hz),1.60-1.70(1H,m),3.38(3H,s),3.54-3.60(4H,m),4.21(1H,d,J=9.8Hz),4.53(2H,s),6.77(1H,d,J=8.6 Hz),7.35-7.94(6H,m) FAB-MS(m/e):565[M+H]⁺

Example 1103

[0595] (R¹:H;R²:H;R³:i-Pr;R⁴:H;Z:Ph;R:3-F-4-HO-Ph)

[0596]¹HNMR(CDCl₃) δ:0.95(3H,d,J=6.6 Hz),1.13(3H,d,J=6.6Hz),1.67-1.74(1H,m),4.21 (1H,d, J=9.8 Hz),6.91-7.93(7H,m)FAB-MS(m/e):342[M+H]⁺

Example 1104

[0597] (R¹:H;R²:H;R³:i-Pr;R⁴:H;Z:Ph;R:3-F-4-MeO-Ph)

[0598]¹HNMR(CDCl₃) δ:0.95(3H,d,J=6.7 Hz),1.13(3H,d,J=6.7Hz),1.63-1.69(1H,m),3.90(3H,s),4.20(1H,d,J=9.8 Hz),6.94-7.92(7H,m)FAB-MS(m/e):356[M+H]⁺

Example 1105

[0599] (R¹:H;R²:H;R³:i-Pr;R⁴:H;Z:Ph;R:3,4-methylenedioxyPh)

[0600]¹HNMR(CDCl₃) δ:0.97(3H,d,J=6.7 Hz),1.13(3H,d,J=6.7Hz),1.65-1.79(1H,m),4.19(1H,d,J=9.9 Hz),5.99(1H,d,J=5.5Hz),6.81(1H,d,J=8.1 Hz),6.86(1H,d,J=1.9 Hz),7.05(1H, dd,J=1.9,8.1Hz),7.33-7.39(1H,m),7.57-7.63(2H,m),7.87-7.93(1H,m)FAB-MS(m/e):352[M+H]⁺

Example 1106

[0601] (R¹:H;R²:H;R¹:i-Pr;R⁴:H;Z:Ph;R:3,4-ethylenedioxyPh)

[0602]¹HNMR(CDCl₃) δ:0.97(3H,d,J=6.6 Hz),1.13(3H,d,J=6.6Hz),1.67-1.72(1H,m),4.18(1H,d,J=10.0 Hz),4.26(4H,s),6.85(1H,d,J=8.4Hz),6.94(1H,dd,J=2.2,8.4 Hz),7.00(1H,d,J=2.2 Hz),7.35-7.90(4H,m)FAB-MS(m/e):366[M+H]⁺

Example 1107

[0603] (R¹:H;R²:H;R³:i-Pr;R⁴:H;Z:Ph;R:3,4-Cl₂-Ph)

[0604]¹HNMR(CDCl₃) δ:0.94(3H,d,J=6.5 Hz),1.13(3H,d,J=6.5Hz),1.53-1.70(1H,m),4.22(1H,d,J=9.4Hz),7.29-7.36(2H,m),7.48(1H,d,J=8.1,Hz),7.59-7.66(3m),7.90-7.94 1H,m)FAB-MS(m/e):376[M+H]⁺

Example 1108

[0605] (R¹:H;R²:H;R³:i-Pr;R⁴:H;Z:Ph;R:3,4-Me₂-Ph)

[0606]¹HNMR(CDCl₃) δ:0.95(3H,d,J=6.7 Hz),1.11(3H,d,J=6.7Hz),1.63-1.71(1H,m),2.25(6H,s),4.18(1H,d,J=10.1 Hz),7.12-7.92(7H,m)FAB-MS(m/e):336[M+H]⁺

Example 1109

[0607] (R¹:H;R²:H;R³:i-Pr;R⁴:H;Z:Ph;R:3,4-F₂-Ph)

[0608]¹HNMR(CDCl₃) δ:0.93(3H,d,J=6.6 Hz),1.13(3H,d,J=6.6Hz),1.64(1H,m),4.22(1H,d, J=9.6Hz),7.19-7.35(4H,m),7.61-7.64(2H,m),7.90-7.94(1H,m)FAB-MS(m/e):344[M+H]⁺

Example 1110

[0609] (R¹:H;R²:H;R³:i-Pr;R⁴:H;Z:Ph;R:3,4-(MeO)₂-Ph)

[0610] ESI-MS(m/e):368[M+H]⁺

Example 1111

[0611] (R¹:H;R²:H;R³:i-Pr;R⁴:H;Z:Ph;R:3,5-(MeO)₂-Ph)

[0612] ESI-MS(m/e):368[M+H]⁺

Example 1112

[0613] (R¹:H;R²:H;R³:i-Pr;R⁴:H;Z:Ph;R:3,5-Me₂-Ph)

[0614] ESI-MS(m/e):336[M+H]⁺

Example 1113

[0615] (R¹:H;R²:H;R³:i-Pr;R⁴:H;Z:Ph;R:3,5-I₂-4-HO-Ph)

[0616]¹HNMR(CDCl₃) δ:0.98(3H,d,J=6.6 Hz),1.15(3H,d,J=6.6Hz),1.61-1.72(1H,m),4.20(1H,d, J=9.9 Hz),5.79(1 H,brs),7.35-7.94(6H,m)FAB-MS(m/e):576[M+H]⁺

Example 1114

[0617] (R¹:H;R²:H:R³:i-Pr;R⁴:H;Z:Ph;R:2,4-I₂-5-HO-Ph)

[0618]¹HNMR(CDCl₃) δ:0.95(3H,d,J=6.6 Hz),1.14(3H,d,J=6.6Hz),1.59-1.66(1H,m),4.26(1H,d,J=9.7Hz),7.21-7.26(1H,m),7.60-7.69(2H,m),7.70(1H,s),7.91-7.95(1H,m),8.14(1H,s)FAB-MS(m/e):576[M+H]⁺

Example 1115

[0619] (R¹:H;Re:H;R³:i-Pr;R⁴:H;Z:Ph;R:3,5-I₂-4-MeO-Ph)

[0620]¹HNMR(CDCl₃) δ:0.96(3H,d,J=6.6 Hz),1.13(3H,d,J=6.6Hz),1.61-1.72(1H,m), 3.89+3.92 (3H,s+s,rotomer),4.19(1H,d,J=9.8Hz),7.34-7.93(6H,m) FAB-MS(m/e):590[M+H]⁺

Example 1116

[0621] (R¹:H;R²:H;R³:i-Pr;R⁴:H;Z:Ph;R:2,4-I₂-5-MeO-Ph)

[0622]¹HNMR(CDCl₃) δ:0.94(3H,d,J=7.1 Hz),1.14(3H,d,J=7.1Hz),1.51-1.64(1H,m),3.99(3H,s),4.26(1H,d,J=9.5Hz),7.22-7.25(1H,m),7.45(1H,s),7.61-7.70(2H,m),7.93-7.95(1H,m),8.23(1H,s) FAB-MS(m/e):590[M+H]⁺

Example 1117

[0623] (R¹:H;R²:H;R³:i-Pr;R⁴:H;Z:Ph;R:2,4,6-Me₃-Ph)

[0624] ESI-MS(m/e):350[M+H]⁺

Example 1118

[0625] (R¹:H;R²:H;R³:i-Pr;R⁴:H;Z:Ph;R:4-HO(CH₂)₃O-3,5-I₂-Ph)

[0626]¹HNMR(CDCl₃) δ:0.99(3H,d,J=6.6 Hz),1.16(3H,d,J=6.6Hz),1.62-1.72(1H,m),2.17(2H,dt,J=5.7 Hz),4.00(2H,t,J=5.7Hz),4.16(2H,t,J=5.7 Hz),4.21(1H,d,J=9.9 Hz),7.38-7.96(6H,m)FAB-MS(m/e):634[M+H]⁺

Example 1119

[0627] (R¹:H;R²:H;R³:i-Pr;R⁴:H;Z:Ph;R:3,5-I₂-4-n-PrNHCOCH₂O-Ph)

[0628]¹HNMR(CDCl₃) δ:0.97(3H,d,J=6.7 Hz),1.00(3H,t,J=7.4Hz),1.15(3H,d,J=6.7 Hz),1.58-1.73(3H,m),3.38(2H,q,J=6.6Hz),4.21(1H,d,J=9.8 Hz),4.49(2H,s),6.79-6.82 (1H,m),7.38-7.40(1H,m),7.62-7.69(2H,m),7.90-7.95(1H,m),7.92(2H,s)FAB-MS(m/e):675[M+H]⁺

Example 1120

[0629] (R¹:H;R²:H;R³:i-Pr;R⁴:H;Z:Ph;R:2-thienyl)

[0630]¹HNMR(CDCl₃) δ:1.04(3H,d,J=6.6 Hz),1.17(3H,d,J=6.6Hz),1.75-1.90(1H,m),4.18(1H,d,J=10.2 Hz),7.02(1H,dd,J=3.6,5.0Hz),7.26(1H,dd,J=1.1,3.6 Hz),7.35(1H,dd,J=1.1, 5.0Hz),7.45-7.55(1H,m),7.56-7.68(2H,m),7.89-7.92(1H,m)FAB-MS(m/e):314[M+H]⁺

Example 1121

[0631] (R¹:H;R²:H;R³:i-Pr;R⁴:H;Z:Ph;R:2-furyl)

[0632]¹HNMR(CDCl₃) δ:1.01(3H,d,J=6.6 Hz),1.21(3H,d,J=6.6Hz),1.92-2.06(1H,m),4.17(1H,d,J=9.7 Hz),6.39(1H,dd,J=1.8,3.3Hz),6.40(1H,d,J=3.3 Hz),7.43(1H,d,J=1.8 Hz),7.58-7.70(3H,m),7.88-7.98(1H,m) FAB-MS(m/e):298[M+H]⁺

Example 1122

[0633] (R¹:H;R²:H;R³:i-Pr;R⁴:H;Z:Ph;R:3-pyridyl)

[0634]¹HNMR(CDCl₃) δ:0.92(3H,d,J=6.7 Hz),1.12(3H,d,J=6.7Hz),1.55-1.70(1H,m),4.24(1H,d,J=9.6Hz),7.32-7.40(2H,m),7.60-7.65(2H,m),7.79-7.83(1H,m),7.92-7.96(1H,m),8.66(1H,d, J=4.6 Hz),8.78(1H,brs) FAB-MS(m/e):309[M+H]⁺

Example 1123

[0635] (R¹:H;R²:H;R³:i-Pr;R⁴:H;Z:Ph;R:2-naphthyl)

[0636] ESI-MS(m/e):358[M+H]⁺

Example 1124

[0637] (R¹:H;R²:H;R³:i-Pr;R⁴:H;Z:Ph;R:5-F-1-naphthyl)

[0638] ESI-MS(m/e):376[M+H]⁺

Example 1125

[0639] (R¹:H;R²:H;R³:i-Pr;R⁴:H;Z:Ph;R:dibenzothiophene-2-yl)

[0640] ESI-MS(m/e):414[M+H]⁺

Example 1126

[0641] (R¹:6-F;R²:H;R³:i-Pr;R⁴:H;Z:Ph;R:Ph)

[0642]¹HNMR(CDCl₃) δ:0.91(3H,d,J=6.6 Hz),1.10(3H,d,J=6.7Hz),1.52-1.67(1H,m),4.22(1H,d, J=9.8 Hz),7.13(1H,d,J=7.8Hz),7.22(1H,dd,J=8.5,8.6 Hz),7.38-7.43(3H,m),7.47-7.51(2H,m),7.57(1H,ddd,J=4.7,7.8,8.5 Hz) FAB-MS(m/e):326[M+H]⁺

Example 1127

[0643] (R¹:7-F;R²:H;R³:i-Pr;R⁴:H;Z:Ph;R:Ph)

[0644]¹HNMR(CDCl₃) δ:0.89(3H,d,J=6.6 Hz),1.10(3H,d,J=6.6Hz),1.64(1H,m),4.20(1H,d, J=9.8 Hz),7.23-7.33(2H,m),7.35-7.51(5H,m),7.54-7.58(1H,m) FAB-MS(m/e):326[M+H]⁺

Example 1128

[0645] (R¹:8-F;R²:H;R³:i-Pr;R⁴:H;Z:Ph;R:Ph)

[0646]¹HNMR(CDCl₃) δ:0.92(3H,d,J=6.6 Hz),1.12(3H,d,J=6.6Hz),1.61-1.65(1H,m),4.20(1H,d,J=9.8Hz),6.98-7.00(1H,m),7.22-7.31(1H,m),7.38-7.49(5H,m),7.90(1H,dd,J=7.6,11.1 Hz) FAB-MS(m/e):326[M+H]⁺

Example 1129

[0647] (R¹:9-F;R²:H;R³:i-Pr;R⁴:H;Z:Ph;R:Ph)

[0648]¹HNMR(CDCl₃) δ:0.89(3H,d,J=6.6 Hz),1.10(3H,d,J=6.7Hz),1.53-1.64(1H,m),4.19(1H,d,J=9.8 Hz),7.24(1H,dd,J=7.8,8.6Hz),7.37-7.41(3H,m),7.50-7.54(2H,m),7.61(1H, dd, J=4.3,7.8,7.8Hz),7.73(1H,d,J=7.8 Hz) FAB-MS(m/e):326[M+H]⁺

Example 1130

[0649] (R¹:6-MeO;R²:H;R³:i-Pr;R⁴:H;Z:Ph;R:Ph)

[0650]¹HNMR(CDCl₃) δ:0.88(3H,d,J=6.7 Hz),1.09(3H,d,J=6.7Hz),1.58-1.68(1H,m),4.01 3H,s),4.21(1H,d,J=9.7 Hz),6.88(1H,d,J=7.3Hz),7.33-7.60(6H,m) FAB-MS(m/e):338[M+H]⁺

Example 1131

[0651] (R¹:9-MeO;R²:H;R³:i-Pr;R⁴:H;Z:Ph;R:Ph)

[0652]¹HNMR(CDCl₃) δ:0.85(3H,d,J=6.6 Hz),1.08(3H,d,J=6.6Hz),1.52-1.59(1H,m),3.69 3H,s),4.15(1H,d,J=9.7 Hz),7.03(1H,dd,1.0,8.0Hz),7.31-7.35(3H,m),7.46-7.59(3H,m), 551H,d, J=7.8 Hz)FAB-MS(m/e):338[M+H]⁺

Example 1132

[0653] (R¹:6-OH;R²:H;R³:i-Pr;R⁴:H;Z:Ph;R:Ph)

[0654]¹HNMR(CDCl₃) δ:0.90(3H,d,J=6.7 Hz),1.10(3H,d,J=6.7Hz),1.52-1.70(1H,m),4.15 1H,d, J=9.7 Hz),6.83(1H,d,7.6Hz),7.00(1H,d,J=8.3 Hz),7.34-7.51 (6H,m),8.03(1H,brs)FAB-MS(m/e):324[M+H]⁺

Example 1133

[0655] (R¹:9-OH;R²:H;R³:i-Pr;R⁴:H;Z:Ph;R:Ph)

[0656]¹HNMR(CDCl₃) δ:0.79(3H,d,J=6.7 Hz),1.06(3H,d,J=6.7Hz),1.60-1.67(1H,m),4.17 1H,d, J=9.5 Hz),7.11(1H,dd,J=1.0,8.2Hz),7.41-7.64(7H,m),9.31(1H,brs) FAB-MS(m/e):324[M+H]⁺

Example 1134

[0657] (R¹:7-NO₂;R²:H;R³:i-Pr;R⁴:H;Z:Ph;R:Ph)

[0658]¹HNMR(CDCl₃) δ:0.93(3H,d,J=6.6 Hz),1.12(3H,d,J=6.6Hz),1.58-1.68(1H,m),4.25 1H,d, J=9.9Hz),7.41-7.55(5H,m),8.45(1H,dd,J=2.2,8.4 Hz),8.74(H,d,J=2.2 Hz)FAB-MS(m/e):353[M+H]⁺

Example 1135

[0659] (R¹:8-NO₂;R²:H;R³:i-Pr;R⁴:H;Z:Ph;R:Ph)

[0660]¹HNMR(CDCl₃) δ:0.93(3H,d,J=6.7 Hz),1.12(3H,d,J=6.7Hz),1.58-1.68(1H,m),4.25 1H,d,J=10.0 Hz),7.42-7.55(5H,m),8.09(1H,d,J=8.3Hz),8.16(1H,d,J=1.8 Hz),8.46(1H,dd, J=1.8,8.3 Hz) FAB-MS(m/e):353[M+H]⁺

Example 1136

[0661] (R¹:9-NO₂;R²:H;R³:i-Pr;R⁴:H;Z:Ph;R:Ph)

[0662]¹HNMR(CDCl₃) δ:0.76(3H,d,J=6.7 Hz),1.10(3H,d,J=6.7Hz),1.45-1.59(1H,m),4.19 1H,d,J=10.0Hz),7.26-7.38(5H,m),7.89(1H,dd,J=7.6,8.1 Hz),8.30(1H,d, J=0.9,.6Hz),.401H, dd,J=0.9,8.1 Hz) FAB-MS(m/e):353[M+H]⁺

Example 1137

[0663] (R¹:6-NHPh;R²:H;R³:i-Pr;R⁴:H;Z:Ph;R:Ph)

[0664]¹HNMR(CDCl₃) δ:0.79(3H,d,J=6.7 Hz),1.11(3H,d,J=6.6Hz),1.50-1.56(1H,m),4.20(1H,d,J=9.5Hz),5.55(1H,s),6.79-6.81(2H,m),6.99-7.01(1H,m),7.19-7.27(2H,m),7.28-7.37(2H,m),7.39-7.44(4H,m),7.46-7.52(2H,m) FAB-MS(m/e):399[M+H]⁺

Example 1138

[0665] (R¹:7-Me₂N;R²:H;R³:i-Pr;R⁴:H;Z:Ph;R:Ph)

[0666]¹HNMR(CDCl₃) δ:0.91(3H,d,J=6.6 Hz),1.10(3H,d,J=6.6Hz),1.55-1.66(1H,m),3.03(6H,s),4.19(1H,d,J=9.9 Hz),6.84(1H,dd,J=2.5,8.6Hz),7.08-7.50(7H,m) FAB-MS(m/e):351[M+H]⁺

Example 1139

[0667] (R¹:7-Me;R²:H;R³:i-Pr;R⁴:H;Z:Ph;R:Ph)

[0668]¹HNMR(CDCl₃) δ:0.91 (3H,d,J=6.6 Hz),1.10(3H,d,J=6.6Hz),1.55-1.65(1H,m),2.45(3H, s),4.20(1H,d,J=9.8 Hz),7.21(1H,d,J=7.9Hz),7.35-7.42(4H,m),7.45-7.50(2H,m),7.70(1H,d, J=0.7 Hz)FAB-MS(m/e):322[M+H]⁺

Example 1140

[0669] (R¹:8-Me;R²:H;R³:i-Pr;R⁴:H;Z:Ph;R:Ph)

[0670]¹HNMR(CDCl₃) δ:0.91(3H,d,J=6.6 Hz),1.09(3H,d,J=6.6Hz),1.55-1.68(1H,m),2.38(3H,s),4.19(1H,d,J=9.8Hz),7.11(1H,s),7.35-7.45(4H,m),7.45-7.52(2H,m), 7.79(1H,d, J=7.6 Hz)FAB-MS(m/e):322[M+H]⁺

Example 1141

[0671] (R¹:7-t-Bu;R²:H;R³:i-Pr;R⁴:H;Z:Ph;R:Ph)

[0672]¹HNMR(CDCl₃) δ:0.92(3H,d,J=6.7 Hz),1.10(3H,d,J=6.7Hz),1.35(9H,s),1.63-1.67(1H,m),4.20(1H,d,J=9.9 Hz),7.26(1H,d,J=8.4Hz),7.37-7.52(5H,m),7.62(1H,dd, J=1.5,8.4 Hz),7.92 (1H,d,J=1.5 Hz)FAB-MS(m/e):364[M+H]⁺

Example 1142

[0673] (R¹:8-t-Bu;R²:H;R³:i-Pr;R⁴:H;Z:Ph;R:Ph)

[0674]¹HNMR(CDCl₃) δ:0.92(3H,d,J=6.7 Hz),1.10(3H,d,J=6.7Hz),1.27(9H,s),1.60-1.65(1H,m),4.19(1H,d,J=9.9 Hz),7.30(1H,d,J=1.6Hz),7.37-7.52(5H,m),7.61(1H,dd,J=1.6, 8.1 Hz),7.83(1H,d,J=8.1 Hz)FAB-MS(m/e):364[M+H]⁺

Example 1143

[0675] (R¹:7-Br;R²:H;R³:i-Pr;R⁴:H;Z:Ph;R:Ph)

[0676]¹HNMR(CDCl₃) δ:0.91 (3H,d,J=6.6 Hz),1.09(3H,d,J=6.65Hz),1.58-1.65(1H,m),4.20(1H, d,J=9.8 Hz),7.40-7.50(6H,m),7.70-7.79(2H,m)FAB-MS(m/e):386/388[M+H]⁺

Example 1144

[0677] (R¹:8-Br;R²:H;R³:i-Pr;R⁴:H;Z:Ph;R:Ph)

[0678]¹HNMR(CDCl₃) δ:0.91(3H,d,J=6.7 Hz),1.10(3H,d,J=6.7Hz),1.61-1.63(1H,m),4.20(1H,d, J=9.8 Hz),7.21(1H,d,J=8.5Hz),7.38-7.49(5H,m),7.70(1H,dd,J=1.9,8.1 Hz),8.03-8.04(1H, m)FAB-MS(m/e):386/388[M+H]⁺

Example 1145

[0679] (R¹:7-Cl;R²:H;R³:i-Pr;R⁴:H;Z:Ph;R:Ph)

[0680]¹HNMR(CDCl₃) δ:0.91 (3H,d,J=6.6 Hz),1.10(3H,d,J=6.6Hz),1.56-1.68(1H,m),4.21(1H,d,J=9.8 Hz),7.27(1H,dd,J=0.6,8.2Hz),7.37-7.43(3H,m),7.44-7.51(2H,m), 7.55(1H, dd,J=1.9, 8.2Hz),7.87(1H,dd,J=0.6,1.9 Hz) FAB-MS(m/e):342[M+H]⁺

Example 1146

[0681] (R¹:8-Cl;R²:H;R³:i-Pr;R⁴:H;Z:Ph;R:Ph)

[0682]¹HNMR(CDCl₃) δ:0.91(3H,d,J=6.6 Hz),1.10(3H,d,J=6.7Hz),1.53-1.72(1H,m),4.20(1H,d,J=9.8 Hz),7.31 (1H,dd,J=0.6, 1.7Hz),7.39-7.48(5H,m),7.56(1H,dd,J=1.7,8.1 Hz), 7.84(1H, dd,J=0.6,8.1 Hz)FAB-MS(m/e):342[M+H]⁺

Example 1147

[0683] (R¹:7-Cl;R²:8-Cl;R³:i-Pr;R⁴:H;Z:Ph;R:Ph)

[0684]¹HNMR(CDCl₃) δ:0.90(3H,d,J=6.6 Hz),1.09(3H,d,J=6.6Hz),1.60-1.64(1H,m),4.19(1H, d, J=9.9 Hz),7.40-7.48(6H,m),7.98(1H,s)FAB-MS(m/e):376[M+H]⁺

Example 1148

[0685] (R¹:6-Cl;R²:9-Cl;R³:i-Pr;R⁴:H;Z:Ph;R:Ph)

[0686]¹HNMR(CDCl₃) δ:0.76(3H,d,J=6.6 Hz),1.09(3H,d,J=6.6Hz),1.49-1.59(1H,m),4.19(1H,d, J=9.6 Hz),7.36-7.48(6H,m),7.52(1H,d,J=8.4 Hz) FAB-MS(m/e):376[M+H]⁺

Example 1149

[0687] (R¹:6-OH;R²:9-I;R³:i-Pr;R⁴:H;Z:Ph;R:Ph)

[0688]¹HNMR(DMSO-d₆) δ:0.64(3H,d,J=6.7 Hz),0.96(3H,d,J=6.7Hz),1.40-1.52(1H,m),4.19(1H,d,J=8.9 Hz),6.82(1H,d,J=8.5Hz),7.30-7.40(5H,m),7.85(1H,d,J=8.5 Hz),10.56 (1H,brs)FAB-MS(m/e):450[M+H]⁺

Example 1150

[0689] (R¹:H;R²:H;R³:i-Pr;R⁴:H;Z:1,2-naphthlyl;R:Ph)

[0690]¹HNMR(CDCl₃) δ:0.80(3H,d,J=6.5 Hz),1.13(3H,d,J=6.5Hz),1.55-1.70(1H,m),4.21(1H,d,J=9.1Hz),7.30-7.40(3H,m),7.40-7.50(3H,m),7.54-7.60(1H,m),7.80(1H,d, J=8.6Hz),7.93(1H,d,J=8.2 Hz),7.94(1H,d,J=8.2 Hz),8.08(1H,d,J=8.2 Hz)FAB-MS(m/e):358[M+H]⁺

Example 1151

[0691] (R¹:H;R²:H;R³:i-Pr;R⁴:H;Z:2,3-naphthlyl;R:Ph)

[0692]¹HNMR(CDCl₃) δ:0.96(3H,d,J=6.1 Hz),1.13(3H,d,J=6.1Hz),1.59-1.67(1H,m),4.28(1H,d, J=10.1Hz),7.34-7.43(3H,m),7.54-7.76(4H,m),7.76(1H,s),7.83-7.85(1H,m),8.04-8.06(1H,m),8.54(1H,s) FAB-MS(m/e):358[M+H]⁺

Example 1152

[0693] (R¹:H;R²:H;R³:i-Pr;R⁴:H;Z:cyclohexenyl;R:Ph)

[0694]¹HNMR(CDCl₃) δ:0.79(3H,d,J=6.0 Hz),1.04(3H,d,J=6.0Hz),1.56-1.80(5H,m),2.28-2.30(4H,m),4.04(1H,d,J=9.0Hz),7.391-7.394(5H,m) FAB-MS(m/e):312[M+H]⁺

[0695] R³ represents an amino acid residue.

Example 1153

[0696] (R¹:H;R²:H;R³:D-Leucine;R⁴:H;Z:Ph;R:Ph)

[0697] ESI-MS(m/e):322[M+H]⁺

Example 1154

[0698] (R¹:H;R²:H;R³:L-Leucine;R⁴:H;Z:Ph:R:Ph)

[0699] ESI-MS(m/e):322[M+H]⁺

Example 1155

[0700] (R¹:H;R²:H;R³:D-NorLeucine;R⁴:H;Z:Ph;R:Ph)

[0701] ESI-MS(m/e):322[M+H]⁺

Example 1156

[0702] (R¹:H;R²:H;R³:L-NorLeucine;R⁴:H;Z:Ph;R:Ph)

[0703] ESI-MS(m/e):322[M+H]⁺

Example 1157

[0704] (R¹:H;R²:H;R³:D-AlloLeucine;R⁴:H;Z:Ph;R:Ph)

[0705] ESI-MS(m/e):322[M+H]⁺

Example 1158

[0706] (R¹:H;R²:H;R³:L-AlloLeucine;R⁴:H;Z:Ph;R:Ph)

[0707] ESI-MS(m/e):322[M+H]⁺

Example 1159

[0708] (R¹:H;R²:H;R³:D-NorValine;R⁴:H;Z:Ph;R:Ph)

[0709] ESI-MS(m/e):308[M+H]⁺

Example 1160

[0710] (R¹:H;R²:H;R³:L-NorValine;R⁴:H;Z:Ph;R:Ph)

[0711] ESI-MS(m/e):308[M+H]⁺

Example 1161

[0712] (R¹:H;R²:H;R³:D-Alanine;R⁴:H;Z:Ph;R:Ph)

[0713] ESI-MS(m/e):280[M+H]⁺

Example 1162

[0714] (R¹:H;R²:H;R³:L-Alanine;R⁴:H;Z:Ph;R:Ph)

[0715] ESI-MS(m/e):280[M+H]⁺

Example 1163

[0716] (R¹:H;R²:H;R³:D-Arginine;R⁴:H;Z:Ph;R:Ph)

[0717] ESI-MS(m/e):365[M+H]⁺

Example 1164

[0718] (R¹:H;R²:H;R³:L-Arginine;R⁴:H;Z:Ph;R:Ph)

[0719] ESI-MS(m/e):365[M+H]⁺

Example 1165

[0720] (R¹:H;R²:H;R³:D-Asparagine;R⁴:H;Z:Ph;R:Ph)

[0721] ESI-MS(m/e):323[M+H]⁺

Example 1166

[0722] (R¹:H;R²:H;R³:L-Asparagine;R⁴:H;Z:Ph;R:Ph)

[0723] ESI-MS(m/e):323[M+H]⁺

Example 1167

[0724] (R¹:H;R²:H;R³:L-Glutamic Acid;R⁴:H;Z:Ph;R:Ph)

[0725] ESI-MS(m/e):338[M+H]⁺

Example 1168

[0726] (R¹:H;R²:H;R³:L-Glutamic Acid;R⁴:H;Z:Ph;R:Ph)

[0727] ESI-MS(m/e):338[M+H]⁺

Example 1169

[0728] (R¹:H;R²:H;R¹:D-Glutamine;R⁴:H;Z:Ph;R:Ph)

[0729] ESI-MS(m/e):337[M+H]⁺

Example 1170

[0730] (R¹:H;R²:H;R³:L-Glutamine;R⁴:H;Z:Ph;R:Ph)

[0731] ESI-MS(m/e):337[M+H]⁺

Example 1171

[0732] (R¹:H;R²:H;R³:D-Histidine;R⁴:H;Z:Ph;R:Ph)

[0733] ESI-MS(m/e):346[M+H]⁺

Example 1172

[0734] (R¹:H;R²:H;R³:L-Histidine;R⁴:H;Z:Ph;R:Ph)

[0735] ESI-MS(m/e):346[M+H]⁺

Example 1173

[0736] (R¹:H;R²:H;R³:D-Methionine;R⁴:H;Z:Ph;R:Ph)

[0737] ESI-MS(m/e):340[M+H]⁺

Example 1174

[0738] (R¹:H;R²:H;R³:L-Methionine;R⁴:H;Z: Ph;R:Ph)

[0739] ESI-MS(m/e):340[M+H]⁺

Example 1175

[0740] (R¹:H;R²:H;R³:D-Tryptophan;R⁴:H;Z:Ph;R:Ph)

[0741] ESI-MS(m/e):395[M+H]⁺

Example 1176

[0742] (R¹:H;R²:H;R³:L-Tryptophan;R⁴:H;Z:Ph;R:Ph)

[0743] ESI-MS(m/e):395[M+H]⁺

Example 1177

[0744] (R¹:H;R²:H;R³:D-Tyrosine;R⁴:H;Z:Ph;R:Ph)

[0745] ESI-MS(m/e):372[M+H]⁺

Example 1178

[0746] (R¹:H;R²:H;R³:L-Tyrosine;R⁴:H;Z:Ph;R:Ph)

[0747]¹HNMR(CDCl₃) δ:2.45(1H,dd,J=11.5,14.5 Hz),3.07(1H,dd,J=4.4,14.5Hz),4.92(1H,dd, J=4.4,11.5 Hz),5.31(1H,brs),6.77(2H,d,J=8.6Hz),6.99(2H,d,J=8.6 Hz),7.34-7.37(1H,m),7.39-7.44(3H,m),7.46-7.50(2H,m),7.55-7.59(2H,m),7.84-7.87(1H,m)

[0748] FAB-MS(m/e):372[M+H]⁺

Example 1179

[0749] (R¹:H;R²:H;R³:D-HomoPhenylalanine;R⁴:H;Z:Ph;R:Ph)

[0750] ESI-MS(m/e):370[M+H]⁺

Example 1180

[0751] (R¹:H;R²:H;R³: L-HomoPhenylalanine;R⁴:H;Z: Ph;R:Ph)

[0752] ESI-MS(rne):370[M+H]⁺

Example 1181

[0753] (R¹:H;R^(2:)H;R¹:D-Leucine;R⁴:H;Z:Ph;R:4-Cl-Ph)

[0754] ESI-MS(m/e):356[M+H]⁺

Example 1182

[0755] (R¹:H;R²:H;R³:L-Leucine;R⁴:H;Z:Ph;R:4-Cl-Ph)

[0756] ESI-MS(m/e):356[M+H]⁺

Example 1183

[0757] (R¹:H;R²:H;R³:D-NorLeucine;R⁴:H;Z:Ph;R:4-Cl-Ph)

[0758] ESI-MS(m/e):356[M+H]⁺

Example 1184

[0759] (R¹:H;R²:H;R³:L-NorLeucine;R⁴:H;Z:Ph;R:4-Cl-Ph)

[0760] ESI-MS(m/e):356[M+H]⁺

Example 1185

[0761] (R¹:H;R²:H;R³:D-AlloLeucine;R⁴:H;Z:Ph:R:4-Cl-Ph)

[0762] ESI-MS(m/e):356[M+H]⁺

Example 1186

[0763] (R¹:H;R²:H;R³:L-AlloLeucine;R⁴:H;Z:Ph;R:4-Cl-Ph)

[0764] ESI-MS(m/e):356[M+H]⁺

Example 1187

[0765] (R¹:H;R²:H;R³:D-NorValine;R⁴:H;Z:Ph;R:4-Cl-Ph)

[0766] ESI-MS(m/e):342[M+H]⁺

Example 1188

[0767] (R¹:H;R²:H;R³:L-NorValine;R⁴:H;Z:Ph;R:4-Cl-Ph)

[0768] ESI-MS(m/e):342[M+H]⁺

Example 1189

[0769] (R¹:H;R²:H;R³:D-Alanine;R⁴:H;Z:Ph;R:4-Cl-Ph)

[0770] ESI-MS(m/e):314[M+H]⁺

Example 1190

[0771] (R¹:H;R²:H;R³:L-Alanine;R⁴:H;Z:Ph;R:4-Cl-Ph)

[0772] ESI-MS(m/e):314[M+H]⁺

Example 1191

[0773] (R¹:H;R²:H;R³:D-Arginine;R⁴:H;Z:Ph;R:4-Cl-Ph)

[0774] ESI-MS(m/e):399[M+H]⁺

Example 1192

[0775] (R¹:H;R²:H;R³:L-Arginine;R⁴:H;Z:Ph;R:4-Cl-Ph)

[0776] ESI-MS(m/e):399[M+H]⁺

Example 1193

[0777] (R¹:H;R²:H;R³:D-Asparagine;R⁴:H;Z:Ph;R:4-Cl-Ph)

[0778] ESI-MS(m/e):357[M+H]⁺

Example 1194

[0779] (R¹:H;R²:H;R³:L-Asparagine;R⁴:H;Z:Ph;R:4-Cl-Ph)

[0780] ESI-MS(m/e):357[M+H]⁺

Example 1195

[0781] (R¹:H;R²:H;R³:D-Glutamic Acid;R⁴:H;Z:Ph;R:4-Cl-Ph)

[0782] ESI-MS(m/e):372[M+H]⁺

Example 1196

[0783] (R¹:H;R²:H;R³:L-Glutamic Acid;R⁴:H;Z:Ph;R:4-Cl-Ph)

[0784] ESI-MS(m/e):372[M+H]⁺

Example 1197

[0785] (R¹:H;R²:H;R³:D-Glutamine;R⁴:H;Z:Ph;R:4-Cl-Ph)

[0786] ESI-MS(m/e):371[M+H]⁺

Example 1198

[0787] (R¹:H;R²:H;R³:L-Glutamine;R⁴:H;Z:Ph;R:4-Cl-Ph)

[0788] ESI-MS(m/e):371[M+H]⁺

Example 1199

[0789] (R¹:H;R²:H;R³:D-Histidine;R⁴:H;Z:Ph;R:4-Cl-Ph)

[0790] ESI-MS(m/e):380[M+H]⁺

Example 1200

[0791] (R¹:H;R²:H;R³:L-Histidine;R⁴:H;Z:Ph;R:4-Cl-Ph)

[0792] ESI-MS(m/e):380[M+H]⁺

Example 1201

[0793] (R¹:H;R²:H;R³:D-Methionine;R⁴:H;Z:Ph;R:4-Cl-Ph)

[0794] ESI-MS(m/e):374[M+H]⁺

Example 1202

[0795] (R¹:H;R²:H;R³:L-Methionine;R⁴:H;Z:Ph;R:4-Cl-Ph)

[0796] ESI-MS(m/e):374[M+H]⁺

Example 1203

[0797] (R¹:H;R²:H;R³:D-Tryptophan;R⁴:H;Z:Ph;R:4-Cl-Ph)

[0798] ESI-MS(m/e):429[M+H]⁺

Example 1204

[0799] (R¹:H;R²:H;R¹:L-Tryptophan;R⁴:H;Z:Ph;R:4-Cl-Ph)

[0800] ESI-MS(m/e):429[M+H]⁺

Example 1205

[0801] (R¹:H;R²:H;R³:D-Tyrosine;R⁴:H;Z:Ph;R:4-Cl-Ph)

[0802] ESI-MS(m/e):406[M+H]⁺

Example 1206

[0803] (R¹:H;R²:H;R³:L-Tyrosine;R⁴:H;Z:Ph;R:4-Cl-Ph)

[0804] ESI-MS(m/e):406[M+H]⁺

Example 1207

[0805] (R¹:H;R²:H;R³:D-HomoPhenylalanine;R⁴:H;Z:Ph;R:4-Cl-Ph)

[0806] ESI-MS(m/e):404[M+H]⁺

Example 1208

[0807] (R¹:H;R²:H;R³:L-HomoPhenylalanine;R⁴:H;Z:Ph;R:4-Cl-Ph)

[0808] ESI-MS(m/e):404[M+H]⁺

Example 1209

[0809] (R¹:H;R²:H;R³:t-Bu;R⁴:H;Z:Ph;R:Ph)

[0810]¹HNMR(CDCl₃) δ:0.90(9H,s),4.29(1H,s),7.30(1H,ddd,J=0.8,3.2,5.6Hz),7.34-7.41(3H,m),7.42-7.44(2H,m),7.54-7.59(2H,m),7.91(1H,ddd,J=0.8,3.2,5.6 Hz)

[0811] ESI-MS(m/e):322[M+H]⁺

Example 1210

[0812] (R¹:H;R²:H;R³:Me₂(OH)C;R⁴:H;Z:Ph;R:Ph)

[0813]¹HNMR(CDCl₃)δ:1.30(3H,s),1.45(3H,s),4.43(1H,s),7.33-7.64(8H,m),7.93(1H,dd, J=6.0,2.6Hz) FAB-MS(m/e):324[M+H]⁺

Example 1211

[0814] (R¹:H;R²:H;R³:Me(MeO)CH;R⁴:H;Z:Ph;R:Ph)

[0815]¹HNMR(CDCl₃) δ:1.54(3H,d,J=6.1 Hz),3.66(3H,s),4.33(1H,d,J=7.3Hz),4.54(1H,dt, J=6.1,7.3 Hz),7.27-7.84(9H,m) FAB-MS(m/e):324[M+H]⁺

Example 1212

[0816] (R¹:H;R²:H;R³:4-HO-Ph;R⁴:H;Z:Ph;R:Ph)

[0817]¹HNMR(CDCl₃) δ:4.95(1H,brs),5.73(1H,s),6.59(2H,d,J=8.4Hz),7.05(2H,d,J=8.4 Hz), 7.22-7.43(6H,m),7.60-7.68(2H,m),7.96-7.98(1H,m)FAB-MS(m/e):358[M+H]⁺

Example 1213

[0818] (R¹:H;R²:H;R³:4-HO-3-I-Ph;R⁴:H;Z:Ph;R:Ph)

[0819]¹HNMR(CDCl₃) δ:5.38(1H,brs),5.68(1H,s),6.76(1H,d,J=8.5Hz),7.14(1H,dd,J=2.2, 8.5Hz),7.30-7.45(7H,m),7.62-7.70(2H,m),7.96-8.00(1H,m)FAB-MS(m/e):484[M+H]⁺

Example 1214

[0820] (R¹:H;R²:H;R³:4-HO-3,5-I₂-Ph;R⁴:FH;Z:Ph;R:Ph)

[0821]¹HNMR(CDCl₃)δ:5.62(1H,s),7.30-7.48(8H,m),7.62-7.80(2H,m),7.97-8.01(1H,m)FAB-MS(m/e):610[M+H]⁺

Example 1215

[0822] (R¹:H;R²:H;R³:4-HO-3-I-PhCH₂;R⁴:H;Z:Ph;R:Ph)

[0823]¹HNMR(CDCl₃) δ:2.45(1H,dd,J=9.8, 14.5 Hz),3.02(1H,dd,J=5.2, 14.5Hz),4.84(1H,dd, J=5.2,9.8Hz),5.61(1H,brs),7.29-7.40(5H,m),7.42-7.43(3H,m),7.57-7.61(2H,m),7.86-7.90(1H,m)FAB-MS(m/e):624[M+H]⁺

Example 1216

[0824] (R¹:H;R²:H;R³:4-HO-3,5-I₂-PhCH₂;R⁴:H;Z:Ph;R:Ph)

[0825]¹HNMR(CDCl₃) δ:2.48(1H,dd,J=10.5,14.5 Hz),3.04(1H,dd,J=4.9, 14.5Hz),4.86(1H,dd, J=4.9, 10.5 Hz),5.31 (1H,brs),6.86(1H,d,J=8.3Hz),7.04(1H,dd,J=2.1,8.3 Hz),7.28(1H,d,J=2.1Hz),7.31-7.36(1H,m),7.41-7.42(5H,m),7.57-7.60(2H,m),7.84-7.89(1H,m)FAB-MS(m/e):498[M+H]⁺

Example 1217

[0826] (R¹:H;R²:H;R³:1-naphthylmethyl;R⁴:H;Z:Ph;R:Ph)

[0827]¹HNMR(CDCl₃) δ:2.54(1H,dd,J=9.8, 14.5 Hz),3.02(1H,dd,J=5.2,14.5Hz),4.84(1H,dd, J=5.2,9.8Hz),5.61(1H,brs),7.32-7.34(1H,m),7.33-7.36(4H,m),7.39-7.43(3H,m),7.57-7.61(2H,m),7.87-7.89(2H,m)

[0828] FAB-MS(m/e):624[M+H]⁺

Example 1218

[0829] (R¹:H;R²:H;R³:4-F-PhCH₂;R⁴:H;Z:Ph;R:Ph)

[0830] ESI-MS(m/e):374[M+H]⁺

Example 1219

[0831] (R¹:H;R²:H;R³: 1-naphthylmethyl;R⁴:H;Z:Ph;R:4-Cl-Ph)

[0832] ESI-MS(m/e):406[M+H]⁺

Example 1220

[0833] (R¹:H;R²:H;R³:4-F-PhCH₂;R⁴:H;Z:Ph;R:4-Cl-Ph)

[0834] ESI-MS(m/e):408[M+H]⁺

Example 1221

[0835] (R¹:H;R²:H;R³:i-Pr;R⁴:Me;Z:Ph;R:Ph)

[0836]¹HNMR(CDCl₃) δ:0.93(3H,d,J=6.8 Hz),0.98(3H,d,J=6.8Hz),1.57-1.59(1H,m),1.70(3R,s),7.31-7.56(8H,m),7.86-7.89(1H,m)

[0837] FAB-MS(m/e):322[M+H]⁺

Example 1222

[0838] (R¹:H;R²:H;R³:Me;R⁴:Me;Z:Ph;R:Ph)

[0839]¹HNMR(CDCl₃)δ:1.27(3H,s),1.87(3H,s),7.35-7.40(4H,m),7.49-7.58(4H,m),7.86-7.89(1H,m)FAB-MS(m/e):294[M+H]⁺

Example 1223

[0840] (R¹:H;R²:H;R³

R⁴:═CH₂(R³ and R⁴ combine to form a ═CH₂ group);Z:Ph;R:Ph)

[0841]¹HNMR(CDCl₃) δ:5.97(2H,d,J=4.3Hz),7.35-7.42(3H,m),7.45-7.53(3H,m),7.57-7.68(2H,m),7.94-7.98(1H,m)FAB-MS(m/e):278[M+H]⁺

Example 1224

[0842] (R¹:H;R²:H;R³ and R⁴:═CHMe(R³ and R⁴ combine to form a ═CHMegroup);Z:Ph;R:Ph)

[0843]¹HNMR(CDCl₃) δ:2.25(3H,d,J=7.3 Hz),6.66(1H,q,J=7.3Hz),7.37-7.42(3H,m),7.48-7.54(3H,m),7.59-7.67(2H,m),7.91-7.93(2H,m)FAB-MS(m/e):292[M+H]⁺

Example 1225

[0844] (R¹:H;R²:H;R³ and R⁴:—(CH₂)₄—(R³ and R⁴ combine to form a (CH₂)₄—group);Z:Ph;R:Ph)

[0845]¹HNMR(CDCl₃)δ:1.50-2.30(7H,m),3.00-3.15(1H,m),7.30-7.42(4H,m),7.43-7.52(2H,m),7.52-7.62(2H,m),7.82-7.92(1H,m) FAB-MS(m/e):320[M+H]⁺

Example 1413

[0846] (R¹:H;R²:H;R³:i-Pr;R⁴:H;Z:2,3-pyrazinyl;R:4-n-PrNHCOCH₂O-Ph)

[0847] FAB-MS(m/e):425[M+H]⁺

Example 1427

[0848] (R¹:H;R²:H;R³:D-Glutamic Acid;R⁴:H;Z:Ph;R:3-Me-4-n-PrNHCO-CH₂OPh)

[0849]¹HNMR(CDCl₃) δ:0.92(3H,t,J=7.4Hz),1.54-1.61(2H,m),2.14-2.24(2H,m),2.28(3H,s),2.58-2.65(2H,m),3.34(2H,q,J=6.6 Hz),4.50(2H,s),4.63(1H,dd,J=5.2,11.0Hz),6.52-6.56(1H,m),6.78(1H,d,J=8.2 Hz),7.27(1H,s),7.32(1H,d,J=8.2Hz),7.35-7.39(1H,m),7.58-7.63(2H, m),7.89-7.92(1H,m)FAB-MS(m/e):467[M+H]⁺

Example 1428

[0850] (R¹:H;R²:H;R³:L-Glutamic Acid;R⁴:H;Z:Ph;R:3-Me-4-n-PrNHCO-CH₂OPh)

[0851]¹HNMR(CDCl₃) δ:0.92(3H,t,J=7.4Hz),1.54-1.61(2H,m),2.14-2.24(2H,m),2.28(3H,s),2.58-2.65(2H,m),3.34(2H,q,J=6.6 Hz),4.50(2H,s),4.63(1H,dd,J=5.2,11.0Hz),6.52-6.56(1H,m),6.78(1H,d,J=8.2 Hz),7.27(1H,s),7.32(1H,d,J=8.2Hz),7.35-7.39(1H,m),7.58-7.63(2H, m),7.89-7.92(1H,m)FAB-MS(m/e):467[M+H]⁺

Example 1429

[0852] (R¹:H;R²:H;R³:(3-Pyridyl)CH₂;R⁴:H;Z:Ph;R:3-Me-4-n-PrNHCOCH₂O-Ph)

[0853]¹HNMR(CDCl₃) δ:0.93(3H,t,J=7.4Hz),1.54-1.68(2H,m),2.27(3H,s),2.62(1H,dd, J=11.0,14.4Hz),3.17(1H,dd,J=4.7,14.4 Hz),3.33(2H,q,J=6.7 Hz),4.90(1H,dd,J=4.5,10.9Hz),6.64-6.68(1H,m),6.82(1H,d,J=8.3 Hz),7.14(1H,d,J=1.8Hz),7.26-7.36(3H,m),7.56-7.64(2H, m),7.72-7.75(2H,m),7.84-7.87(1H,m)FAB-MS(m/e):486[M+H]⁺

Example 1430

[0854] (R¹:H;R²:H;R³:i-Pr;R⁴:H;Z:Ph;R:4-n-PrNHCOCH₂O-3-CH₂═CH-Ph)

[0855]¹HNMR(CDCl₃) δ:0.92(3H,d,J=6.5 Hz),0.95(3H,t,J=7.3Hz),1.12(3H,d,J=6.5 Hz),1.23-1.35(1H,m),1.50-1.67(2H,m),3.33(2H,q,J=6.8Hz),4.21(1H,d,J=9.9 Hz),4.53(2H,s),5.40(1H,d,J=11.2 Hz),5.76(1H,d,J=17.7Hz),6.44-6.48(1H,m),6.85(1H,d,J=8.8 Hz),6.96(1H, dd,J=11.2,17.7Hz),7.27-7.40(3H,m),7.59-7.61(2H,m),7.90-7.93(1H,m)FAB-MS(m/e):449[M+H]⁺

Example 1431

[0856] (R¹:H;R²:H;R³:i-Pr;R⁴:H;Z:Ph;R:4-n-PrNHCOCH₂O-3-(2-Pyridyl)-Ph)

[0857]¹HNMR(CDCl₃) δ:0.82(3H,t,J=7.4 Hz),0.98(3H,d,J=6.6Hz).1.14(3H,d,J=6.6 Hz),1.43-1.55(2H,m),1.65-1.77(1H,m),3.25(2H,q,J=6.5Hz),4.23(1H,d,J=9.9 Hz),4.62(2H,d, J=14.9 Hz),7.05(1H,d,J=8.7Hz),7.32-7.40(2H,m),7.50-7.63(5H,m),7.81-7.86(1H,m),7.90-7.92(1H,m),8.195-8.197(1H,m)FAB-MS(m/e):500[M+H]⁺

Example 1432

[0858] (R¹:H;R²:H;R³:i-Pr;R⁴:H;Z:Ph;R:4-n-PrNHCOCH₂O-3-(3-Pyridyl)-Ph)

[0859]¹HNMR(CDCl₃) δ:0.80(3H,t,J=7.4 Hz),0.99(3H,d,J=6.6Hz),1.15(3H,d,J=6.6 Hz),1.37-1.42(2H,m),1.65-1.75(1H,m),3.18(2H,q,J=6.7Hz),4.24(1H,d,J=9.9 Hz),4.50(2H,d, J=14.2Hz),6.10-6.12(1H,m),6.99(1H,d,J=8.7 Hz),7.37-7.42(2H,m),7.44(1H,d,J=2.4Hz), 7.56-7.65(3H,m),7.77(1H,dd,J=1.8,7.8Hz),7.91-7.94(1H,m),8.63-8.72(2H,m) FAB-MS(m/e):500[M+H]⁺

Example 1433

[0860] (R¹:H;R²:H;R³:i-Pr;R⁴:H;Z:Ph;R:4-n-PrNHCOCH₂O-3-(4-Pyridyl)-Ph)

[0861]¹HNMR(CDCl₃) δ:0.82(3H,t,J=7.4 Hz),0.98(3H,d,J=6.6Hz),1.15(3H,d,J=6.6 Hz),1.38-1.48(2H,m),1.64-1.74(1H,m),3.19(2H,q,J=6.4Hz),4.24(1H,d,J=9.9 Hz),4.52(2H,d, J=14.2Hz),6.14-6.16(1H,m),6.99(1H,d,J=8.6 Hz),7.36-7.44(3H,m),7.47(1H,d,J=2.4Hz), 7.54-7.65(3H,m),7.91-7.94(1H,m),8.69-8.76(2H,m)FAB-MS(m/e):500[M+H]+

Example 1434

[0862] (R¹:H;R²:H;R³:i-Pr;R⁴:H;Z:Ph;R:3-Ph-4-n-PrNHCOCH₂O-Ph)

[0863]¹HNMR(CDCl₃) δ:0.79(3H,t,J=7.4 Hz),0.99(3H,d,J=6.6Hz),1.15(3H,d,J=6.6 Hz),1.26-1.40(2H,m),1.65-1.76(1H,m),3.14(2H,q,J=7.1Hz),4.23(1H,d,J=9.9 Hz),4.48(2H,d, J=14.3Hz),6.25(1H,s),6.94(1H,d,J=8.6Hz),7.37-7.45(7H,m),7.51(1H,dd,J=2.5,8.6 Hz),7.57-7.62(2H,m),7.89-7.92(1H,m) FAB-MS(m/e):499[M+H]⁺

Example 1435

[0864] (R¹:H;R^(2:)H;R³:i-Pr;R⁴:H;Z:Ph;R:3-Et-4-n-PrNHCOCH₂O-Ph)

[0865]¹HNMR(CDCl₃) δ:0.93(3H,t,J=7.4 Hz),0.94(3H,d,J=6.6Hz),1.11(3H,d,J=6.6 Hz),1.21(3H,t,J=7.5Hz),1.53-1.68(3H,m),2.61-2.73(2H,m),3.33(2H,q,J=6.6 Hz),4.20(1H,d, J=9.9Hz),4.50(2H,s),6.48-6.49(1H,m),6.80(1H,d,J=8.6 Hz),7.28(1H,d,J=2.2Hz),7.34(1H,dd,J=2.2,8.6Hz),7.341-7.347(1H,m),7.58-7.62(2H,m),7.90-7.93(1H,m)FAB-MS(m/e):451[M+H]⁺

Example 1436

[0866] (R¹:H;R²:H;R³:i-Pr;R⁴:H;Z:Ph;R:3-n-Bu-4-n-PrNHCOCH₂O-Ph)

[0867]¹HNMR(CDCl₃) δ:0.92(3H,t,J=7.3 Hz),0.93(3H,t,J=7.3Hz),1.11(3H,d,J=6.8 Hz),1.24-1.42(6H,m),1.28(3H,d,J=6.8Hz),1.53-1.64(1H,m),2.51-2.71(2H,m),3.33(2H,q, J=6.6 Hz),4.20(1H,d,J=9.9Hz),4.49(2H,s),6.47-6.49(1H,m),6.79(1H,d,J=8.4 Hz),7.25(1H,d,J=2.4Hz),7.33(1H,dd,J=2.4,8.4Hz),7.33-7.36(1H,m),7.56-7.61(2H,m),7.90-7.92(1H,m)FAB-MS(m/e):479[M+H]⁺

Example 1437

[0868] (R¹:H;R²:H;R³:i-Pr;R⁴:H;Z:Ph;R:3-MeO-6-Me-Ph)

[0869]¹HNMR(CDCl₃) δ:0.84(3H,d,J=6.2 Hz),1.11(3H,d,J=6.2Hz),1.61-1.68(1H,m),1.73(3H,s),3.86(3H,s),4.23(1H,d,J=9.6Hz),6.82(1H,dd,J=2.1,8.2 Hz),6.99(1h,d,J=8.2Hz),7.30-7.31(1H,m),7.46(1H,d,J=2.1 Hz),7.60-7.61 (2H,m),7.92-7.95(1H,m)FAB-MS(m/e):352[M+H]⁺

Example 1438

[0870] (R¹:H;R²:H;R³:i-Pr;R⁴:H;Z:Ph;R:3-HO-6-Me-Ph)

[0871]¹HNMR(CDCl₃) δ:0.84(3H,d,J=6.6 Hz),1.10(3H,d,J=6.6Hz),1.62-1.67(1H,m),1.71(3H,s),4.24(1H,d,J=9.5Hz),5.72-5.73(1H,m),6.81(1H,dd,J=2.3,8.0 Hz),6.94(1H,d, J=8.0Hz),7.28-7.31(1H,m),7.42(1H,d,J=2.3 Hz),7.59-7.64(2H,m),7.93-7.96(1H,m)FAB-MS(m/e):338[M+H]⁺

Example 1439

[0872] (R¹:H;R²:H;R³:i-Pr;R⁴:H;Z:Ph;R:6-Me-3-n-PrNHCOCH₂O-Ph)

[0873]¹HNMR(CDCl₃) δ:0.82(3H,d,J=6.7 Hz),0.98(3H,t,J=7.4Hz),1.12(3H,d,J=6.7 Hz),1.58-1.72(3H,m),1.75(3H,s),3.37(2H,q,J=6.7Hz),4.26(1H,d,J=9.4 Hz),4.51-4.52(2H,m),6.70-6.71(1H,m),6.81(1H,dd,J=2.7,8.3 Hz),7.04(1H,d,J=8.3Hz),7.27-7.28(1H,m),7.30(1H,d, J=2.7 Hz),7.54-7.65(2H,m),7.94-7.96(1H,m)FAB-MS(m/e):437[M+H]⁺

Example 2002

[0874]3-(1-Methylethyl)-9b-phenyl-1H-imidazo[2,1-a]isoindole-2,5(3H-9bH)-dione(compound of R¹:H;R²:H;R³:i-Pr;R⁴:H;R⁵:H;Z:Ph;R:Ph in the generalformula [I-2])

[0875] 1-Hydroxybenzotriazole hydrate (100 mg, 0.73 mmol),1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (113 mg,0.58 mmol) and 28% ammonia water (3 ml) were added to a solution ofN-t-butoxycarbonyl-D-valine (106 mg, 0.49 mmol) in N,N-dimethylformamide(1 ml) at room temperature, and the reaction mixture was stirred at roomtemperature for 12 hours. Water and ethyl acetate were added to thereaction mixture, and the organic layer was dried and concentrated underreduced pressure. The resulting residue was purified by flash silica gelcolumn chromatography to obtain an amide (80 mg, yield: 76%). The amide(80 mg, 0.37 mmol) was dissolved in a solution of 4N hydrochloric acidin 1,4-dioxane (2 ml), and the reaction mixture was stirred at roomtemperature for 1 hour and concentrated under reduced pressure.1-Hydroxybenzotriazole hydrate (60 mg, 0.63 mmol),1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (85 mg, 0.44mmol) and triethylamine (0.12 ml, 0.85 mmol) were successively added toa solution of the resulting residue and 2-benzoylbenzoic acid (83 mg,0.37 mmol) in dimethylformamide (2 ml) at room temperature, and thereaction mixture was stirred at room temperature for 12 hours. Water andethyl acetate were added to the reaction mixture, and the organic layerwas dried and concentrated under reduced pressure. The resulting residuewas purified by flash silica gel column chromatography to obtain acondensed compound (130 mg, yield: 99%). p-Toluenesulfonic acid (10 mg)was added to a solution of the obtained condensed compound (13 mg, 0.040mmol) in toluene (2 ml) at room temperature, and the reaction mixturewas stirred under reflux with heating for 4 hours. The reaction mixturewas concentrated under reduced pressure, the resulting residue wassubjected three times to azeotropic distillation with toluene, and thereaction mixture was concentrated under reduced pressure. The resultingresidue was purified by silica gel column chromatography (hexane:ethylacetate=2:1) to obtain the captioned compound (2.0 mg, yield: 16%) ascolorless oily matter.

[0876]¹HNMR(CDCl₃) δ:0.81 (3H,d,J=6.6 Hz),1.14(3H,d,J=6.6Hz),1.70-1.83(1H,m),4.15(1H,d,J=8.6Hz),7.30-7.35(5H,m),7.50-7.54(2H,m),7.89-7.93(1H,m),8.09(1H,brs)FAB-MS(m/e):307[M+H]⁺

[0877] In the same manner as in Example 2002, compounds of Examples2011, 2050, 2074, 2467, 2471, 2472 and 2474 corresponding to thecompound numbers of the compounds of the general formula [I-2] in theaforementioned compound lists were obtained. Physical constants of thesecompounds are shown below.

Example 2011

[0878] (R¹:H;R²:H;R³:i-Pr;R⁴:H;R⁵:H;Z:Ph;R:4-MeO-Ph)

[0879]¹HNMR(CDCl₃) δ:0.86(3H,d,J=6.8 Hz),1.19(3H,d,J=6.8Hz),1.77-1.85(1H,m),3.79(3H,s),4.16(1H,d,J=8.6 Hz),6.84(2H,d,J=8.9Hz),7.22-7.88(6H,m),9.55(1H,brs) ESI-MS(m/e):337[M+H]⁺

Example 2050

[0880] (R¹:H;R²:H;R³:i-Pr;R⁴:H;R⁵:H;Z:Ph;R:3-NH₂-4-Cl-Ph)

[0881]¹HNMR(CDCl₃) δ:0.89(3H,d,J=6.7 Hz),1.17(3H,d,J=6.7Hz),1.77-1.88(1H,m),4.13(1H,d,J=8.7 Hz),6.67(1H,dd,J=2.2,8.3Hz),6.77(1H,d,J=2.2 Hz),7.19(1H,d,J=8.3 Hz),7.21-7.88 (4H,m),9.02(1H,s)ESI-MS(m/e):356[M+H]⁺

Example 2074

[0882] (R¹:H;R²:H;R³:i-Pr;R⁴:H;R⁵:H;Z:Ph;R:3-I-4-n-PrNHCOCH₂O-Ph)

[0883]¹HNMR(CDCl₃) δ:0.86(3H,d,J=6.7 Hz),0.98(3H,t,J=7.4Hz),1.17(3H,d,J=6.7 Hz),1.55-1.78(3H,m),3.35(2H,q,J=7.0Hz),4.16(1H,d,J=8.8Hz),4.50(2H,s),6.73(1H,d,J=8.6Hz),6.92(1H,brs),7.16-7.93(6H,m),8.98(1H,brs) FAB-MS(m/e):548[M+H]⁺

Example 2467

[0884](R¹:H;R²:H;R³:i-Pr;R⁴:H;R⁵:H;Z:Ph;R:4-n-PrNHCOCH₂O-pyrimidin-5-yl)FAB-MS(m/e):424[M+H]⁺

Example 2471

[0885] (R¹:H;R²:H;R³:i-Pr;R⁴:H;R⁵:Me;Z:Ph;R:4-n-PrNHCOCH₂O-Ph)

[0886]¹HNMR(CDCl₃) δ:0.76(3H,d,J=6.6 Hz),0.91 (3H,d,J=7.4Hz),1.17(3H,d,J=6.6 Hz),1.52-1.68(3H,m),3.13(3H,s),3.31 (2H,dt,J=6.6,7.3Hz),4.03(1H,d,J=10.0 Hz),4.48(2H,s),6.53(1H,brs),6.85-8.00(8H,m)FAB-MS(m/e):436[M+H]⁺

Example 2472

[0887](R¹:H;R^(2:)H;R³:i-Pr;R⁴:H;R⁵:n-PrNHCOCH₂;Z:Ph;R:4-n-PrNHCO-CH₂OPh)

[0888]¹HNMR(CDCl₃) δ:0.61 (3H,t,J=7.4 Hz),0.81(3H,d,J=6.5Hz),0.93(3H,t,J=7.4 Hz), 1.01-1.11 (2H,m),1.20(3H,d,J=6.5Hz),1.51-1.68(3H,m),2.83-2.97(2H,m),3.32(2H,t,J=7.3 Hz),4.17(1H,d,J=10.5Hz),4.33(2H,d,J=16.2Hz),4.50(2H,s),5.69(1H,brs),6.52(1H,brs),6.87-8.00(8H,m)FAB-MS(m/e):521[M+H]⁺

Example 2474

[0889](R¹:H;R²:H;R³:i-Pr;R⁴:H;R⁵:MeSO₂NHCOCH₂;Z:Ph;R:4-n-PrNHCO-CH₂O-Ph)

[0890] FAB-MS(m/e):557[M+H]⁺

Example 3011

[0891]9b-(4-Methoxyphenyl)-3-(1-methylethyl)-1H-pyrrolo[2.1-a]isoindole-2,5(3H,9bH)-dione(compound of R¹:H;R²:H;R³:i-Pr;R⁴:H;R⁶:H;Z:Ph;R:4-MeO-Ph in the generalformula [I-3])

[0892] Triethylamine (55 ml, 390 mmol) and ethyl chloroformate (13 ml,140 mmol) were added to a solution of N-t-butoxycarbonyl-D-valine (25 g,120 mmol) in tetrahydrofuran (500 ml) at −40° C., the reaction mixturewas stirred at −40° C. for 2 hours, N,O-dimethylhydroxylaminehydrochloride (23 g, 230 mmol) was added at −40° C., the mixture wasstirred at 0° C. for 1 hour, and aqueous ammonium chloride solution wasadded. The mixture was extracted with ethyl acetate, and the organiclayer was washed with aqueous saturated sodium chloride solution, driedand concentrated under reduced pressure. The resulting residue waspurified by silica gel column chromatography (hexane:ethyl actate=7:3)to obtain an amide (18 g, yield: 61%). A solution (56.6 mmol) ofmethylmagnesium bromide (3.0 M) in diethyl ether (19.0 ml) was addeddropwise to a solution of the amide (4.9 g, 18.9 mmol) intetrahydrofuran (100 ml) at −70° C., the reaction mixture was stirred atroom temperature for 2 hours, and then aqueous ammonium chloridesolution was added to the reaction mixture. The mixture was extractedwith ethyl acetate, and the organic layer was washed with aqueoussaturated sodium chloride solution, dried and concentrated under reducedpressure. The resulting residue was purified by silica gel columnchromatography (hexane:ethyl acetate=8:1) to obtain a ketone (2.0 g,yield: 50%).

[0893] The obtained ketone (2.0 g, 0.22 mmol) was dissolved in asolution of 4N hydrochloric acid in 1,4-dioxane (20 ml) at roomtemperature, and the reaction mixture was stirred at room temperaturefor 1 hour and concentrated under reduced pressure to obtain an aminehydrochloride (1.4 g, yield: 99%). The amine hydrochloride (510 mg. 3.4mmol) was dissolved in methylene chloride (32 ml), and1-hydroxybenzotriazole hydrate (590 mg, 4.4 mmol),2-(4-methoxybenzoyl)benzoic acid (860 mg, 3.4 mmol).1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (840 mg, 4.4mmol) and triethylamine (1.8 ml, 13.5 mmol) were successively added tothe reaction mixture at room temperature. The reaction mixture wasstirred at room temperature for 12 hours, and water was added to thereaction mixture. The mixture was extracted with ethyl acetate, and theorganic layer was washed with aqueous saturated sodium bicarbonatesolution and aqueous saturated sodium chloride solution, dried andconcentrated under reduced pressure. The resulting residue was purifiedby silica gel column chromatography (hexane:ethyl acetate=3:2) to obtaina condensed product (990 mg, yield: 83%). Triethylamine (2.1 ml, 15mmol) and trimethylsilyl trifluoromethanesulfonate (2.7ml, 15 mmol) weresuccessively added to a solution of the obtained condensed compound (890mg, 2.5 mmol) in methylene chloride (50 ml), and the reaction mixturewas stirred at room temperature for 2 hours. A boron trifluoride-diethylether complex (6.4 ml, 50 mmol) was added at −70° C., and the reactionmixture was stirred at room temperature for 12 hours. Water was added tothe reaction mixture, and the mixture was extracted with chloroform. Theorganic layer was washed with aqueous saturated ammonium chloridesolution and aqueous saturated sodium chloride solution, dried andconcentrated under reduced pressure. The obtained residue was purifiedby silica gel column chromatography (hexane:ethyl acetate=4:1) to obtainthe diastereomer A of the captioned compound (94 mg, yield: 11%) ascolorless oily matter and the diastereomer B thereof (306 mg, yield:36%) as colorless oily matter.

[0894] Diastereomer A

[0895]¹HNMR(CDCl₃) δ:0.86(3H,d,J=7.0 Hz),1.19(3H,d,J=7.0Hz),2.59(1H,d,J=15.9 Hz), 3.44(1H,d,J=15.9Hz),3.63-3.71(1H,m),3.76(3H,s),3.78(1H,d,J=3.2 Hz),6.83(2H,d, J=8.9Hz),7.23-7.28(1H,m),7.35-7.37(1H,m),7.43-7.54(2H,m),7.87-7.90(1H,m)ESI-MS(m/e):336[M+H]⁺

[0896] Diastereomer B

[0897]¹HNMR(CDCl₃) δ:0.85(3H,d,J=6.7 Hz),1.09(3H,d,J=6.7Hz),1.50-1.70(1H,m),2.53(1H,d,J=17.4 Hz),3.60(1H,d,J=17.4Hz),3.79(3H,s),4.01(1H,d,J=9.6 Hz),6.84(2H,d,J=9.0Hz),7.14-7.24(1H,m),7.21 (2H,d,J=9.0 Hz),7.45-7.54(2H,m),7.90-7.93(1H,m)ESI-MS(m/e):336[M+H]⁺

[0898] In the same manner as in Example 3011, compounds of Examples3001, 3002, 3007, 3014, 3015, 3020, 3023, 3024, 3033, 3039, 3047, 3050,3051, 3056, 3057, 3058, 3061, 3063, 3065, 3072, 3073, 3074, 3082, 3092,3093, 3094, 3095, 3096, 3103, 3104, 3107, 3112, 3115, 3117, 3126, 3129,3134, 3226, 3241, 3246, 3258, 3266, 3296, 3307, 3319, 3412, 3418, 3464,3472, 3473, 3474, 3475, 3476, 3477, 3478, 3479, 3480, 3481, 3482, 3485,3486, 3487, 3488, 3489, 3492, 3499, 3500, 3501, 3509, 3510, 3511, 3515and 3516 corresponding to the compound numbers of the compounds of thegeneral formula [I-3a], the compounds of the general formula [I-3b], thegeneral formula [I-3c] or the compounds of the general formula [I-3d] inthe aforementioned compound lists were obtained. Physical constants ofthese compounds are shown below.

Example 3001

[0899] (R¹:H;R²:H;R³:i-Pr;R⁴:H;R⁶:H;Z:Ph;R:2-MeO-Ph)

[0900] Diastereomer A

[0901]¹HNMR(CDCl₃) δ:0.85(3H,d,J=7.0 Hz),1.21(3H,d,J=7.0Hz),2.61(1H,d,J=16.7 Hz), 3.67-3.78(1H,m),3.86(1H,d,J=16.7Hz),3.87(1H,d,J=3.2 Hz),4.01(3H,s),6.87(1H,t, J=7.4 Hz),6.94(1H,d,J=8.0Hz),7.22-7.28(2H,m),7.41-7.50(2H,m),7.83(1H,dd,J=1.6, 7.4Hz),7.90(1H,d,J=6.3 Hz) ESI-MS(m/e):336[M+H]⁺

[0902] Diastereomer B

[0903]¹HNMR(CDCl₃) δ:1.13(6H,d,J=6.6Hz),1.69-1.74(1H,m),2.64(1H,d,J=18.1 Hz),3.89(3H,brs),3.97(1H,d,J=18.1Hz),4.00(1H,d,J=10.3 Hz),6.88(1H,t,J=7.6 Hz),6.94(1H,d,J=8.2Hz),7.30(1H,t,J=8.2 Hz),7.41-7.50(3H,m),7.61(1H,brs),7.86(1H,d,J=6.5 Hz)ESI-MS(m/e):336[M+H]⁺

Example 3002

[0904] (R¹:H;R²:H;R³:i-Pr;R⁴:H;R⁶:H;Z:Ph;R:Ph)

[0905]¹HNMR(CDCl₃) δ:0.87(3H,d,J=6.7 Hz),1.09(3H,d,J=6.6Hz),1.49-1.70(1H,m),2.58(1H,d,J=17.6 Hz),3.66(1H,d,J=7.6Hz),4.03(1H,d,J=9.6Hz),7.12-7.21(1H,m),7.25-7.39(5H,m),7.42-7.56(2H,m),7.89-7.97(1H,m)FAB-MS(m/e):306[M+H]⁺

Example 3007

[0906] (R¹:H;R²:H;R³:i-Pr;R⁴:H;R⁶:H;Z:Ph;R:4-HO-Ph)

[0907]¹HNMR(CDCl₃) δ:0.84(3H,d,J=6.7 Hz),1.09(3H,d,J=6.7Hz),1.51-1.64(1H,m),2.52(1H, d,J=17.3 Hz),3.59(1H,d,J=17.3Hz),4.01(1H,d,J=9.5Hz),5.17(1H,brs),6.79(2H,d,J=8.8Hz),7.15-7.19(1H,m),7.16(2H,d,J=8.8Hz),7.46-7.54(2H,m),7.90-7.93(1H,m) ESI-MS(m/e):322[M+H]⁺

Example 3014

[0908] (R¹:H;R²:H;R³:i-Pr;R⁴:H;R⁶:H;Z:Ph;R:4-t-BuO₂CCH₂O-Ph)

[0909]¹HNMR(CDCl₃) δ:0.83(3H,d,J=6.6 Hz),1.08(3H,d,J=6.6Hz),1.45-1.46(9H,m),1.49-1.67(1H,m),2.53(1H,d,J=17.3Hz),3.59(1H,d,J=17.3 Hz),4.01(1H,d,J=9.6Hz),4.48-4.49(2H,m),6.83(2H,d,J=8.9 Hz),7.15-7.24(1H,m),7.20(2H,d,J=8.9Hz),7.45-7.55(2H,m), 7.90-7.93(1H,m) FAB-MS(m/e):436[M+H]⁺

Example 3015

[0910] (R¹:H;R²:H;R³:i-Pr;R⁴:H;R⁶:H;Z:Ph;R:4-HO₂CCH₂O-Ph)

[0911]¹HNMR(CDCl₃) δ:0.83(3H,d,J=6.6 Hz),1.08(3H,d,J=6.6Hz),1.47-1.59(1H,m),2.56(1H,d,J=17.2 Hz),3.61(1H,d,J=17.2Hz),4.02(1H,d,J=9.6 Hz),4.67(2H,s),6.87(2H,d,J=8.9Hz),7.17(1H,dd,J=1.4,6.2 Hz),7.22(2H,d,J=8.9Hz),7.46-7.56(2H,m),7.93(1H,dd,J=1.8, 6.2 Hz),8.65(1H,brs)FAB-MS(m/e):380[M+H]⁺

Example 3020

[0912] (R¹:H;R^(2:)H;R³:i-Pr;R⁴:H;R⁶:H;Z:Ph;R:4-HOC(Me)₂(CH₂)₂O-Ph)

[0913]¹HNMR(CDCl₃) δ:0.87(3H,d,J=6.6 Hz),1.12(3H,d,J=6.6Hz),1.32(6H,s),1.50-1.62(1H,m),1.99(2H,t,J=6.3 Hz),2.55(1H,d,J=16.0Hz),3.62(1H,d,J=16.0 Hz),4.02(1H,d,J=9.5 Hz),4.17(2H,t,J=6.3Hz),6.86(1H,d,J=8.8 Hz),7.18-7.92(6H,m) FAB-MS(m/e):408[M+H]⁺

Example 3023

[0914] (R¹:H;R²:H;R³:i-Pr;R⁴:H;R⁶:H;Z:Ph;R:4-EtNHCOCH₂O-Ph)

[0915] FAB-MS(m/e):407[M+H]⁺

Example 3024

[0916] (R¹:H;R¹:H;R¹:i-Pr;R¹:H;R¹:H;Z:Ph;R:4-n-PrNHCOCH₂O-Ph)

[0917]¹HNMR(CDCl₃) δ:0.84(3H,d,J=6.6 Hz),0.90(3H,t,J=7.4Hz),1.09(3H,d,J=6.6 Hz),1.49-1.61(3H,m),2.55(1H,d,J=17.4Hz),3.30(2H,q,J=6.8 Hz),3.60(1H,d,J=17.4 Hz),4.02(1H,d, J=9.5Hz),4.47(2H,s),6.53(1H,brs),6.88(2H,d,J=9.0 Hz),7.16(1H,dd,J=2.2,5.7Hz),7.27(2H,d,J=9.0 Hz),7.46-7.55(2H,m),7.92(1H,dd,J=2.0,5.1 Hz)FAB-MS(m/e):421[M+H]⁺

Example 3033

[0918] (R¹:H;R^(2:):H;R³:i-Pr;R⁴:H;R⁶:H;Z:Ph;R:4-n-PrNHCOCH═CH-Ph)FAB-MS(m/e):417[M+H]⁺

Example 3039

[0919] (R¹:H;R²:H;R³:i-Pr;R⁴:H;R⁶:H;Z:Ph;R:3-HO₂COCH₂O-Ph)

[0920] FAB-MS(m/e):380[M+H]⁺

Example 3047

[0921] (R¹:H;R²:H;R³:i-Pr;R⁴:H;R⁶:H;Z:Ph;R:4-Cl-3-NO₂-Ph)

[0922] FAB-MS(m/e):385[M+H]⁺

Example 3050

[0923] (R¹:H;R²:H;R³:i-Pr;R⁴:H;R⁶:H;Z:Ph:R:3-NH₂-4-Cl-Ph)

[0924] FAB-MS(m/e):355[M+H]⁺

Example 3051

[0925] (R¹:H;R²:H;R³:i-Pr;Re:H;R⁶:H;Z:Ph;R:3-Cl-4-MeO-Ph)FAB-MS(m/e):370[M+H]⁺

Example 3056

[0926] (R¹:H;R²:H;R³:i-Pr;R⁴:H;R¹:H;Z:Ph;R:3-F-4-Me-Ph)

[0927]¹HNMR(CDCl₃) δ:0.90(3H,d,J=6.7 Hz),1.10(3H,d,J=6.7Hz),1.53-1.65(1H,m),2.24(3H,s),2.57(1H,d,J=17.5 Hz),3.56(1H,d,J=17.5Hz),4.02(1H,d,J=9.7 Hz),6.95(1H,dd,J=1.9,10.7 Hz),7.02(1H,dd,J=1.9,7.9Hz),7.14(1H,d,J=7.9 Hz),7.17-7.20(1H,m),7.47-7.55(2H,m),7.90-7.93(1H,m)ESI-MS(m/e):338[M+H]⁺

Example 3057

[0928] (R¹:H;R²:H;R³:i-Pr;R⁴:H;R⁶:H;Z:Ph;R:3-Br-4-HO-Ph)

[0929]¹HNMR(CDCl₃) δ:0.88(3H,d,J=6.6 Hz),1.11(3H,d,J=6.6Hz),1.53-1.70(1H,m),2.55(1H,d,J=17.4 Hz),3.55(1H,d,J=17.4Hz),4.02(1H,d,J=9.6 Hz),5.81(1H,brs),6.98(1H,d,J=8.5Hz),7.15-7.20(2H,m),7.42(1H,d,J=2.3 Hz),7.48-7.57(2H,m),7.91-7.94(1H,m)FAB-MS(m/e):400/402[M+H]⁺

Example 3058

[0930] (R¹:H;R²:H;R³:i-Pr;R⁴:H;R⁶:H;Z:Ph;R:3-Br-4-MeO-Ph)

[0931]¹HNMR(CDCl₃) δ:0.89(3H,d,J=6.6 Hz),1.11(3H,d,J=6.6Hz),1.51-1.65(1H,m),2.55(1H,d,J=17.4 Hz),3.56(1H,d,J=17.4Hz),3.88(3H,s),4.02(1H,d,J=9.6Hz),6.84(1H,d,J=8.6Hz),7.17-7.25(2H,m),7.47-7.56(3H,m),7.91-7.94(1H,m)FAB-MS(m/e):414/416[M+H]⁺

Example 3061

[0932] (R¹:H;R²:H;R³:i-Pr;R⁴:H;R⁶:H;Z:Ph;R:4-HO-3-I-Ph)

[0933] FAB-MS(m/e):448[M+H]⁺

Example 3063

[0934] (R¹:H;R²:H;R³:i-Pr;R⁴:H;R⁶:H;Z:Ph;R:3-I-4-MeO-Ph)

[0935]¹HNMR(CDCl₃) δ:1.11(3H,d,J=6.6 Hz),1.27(3H,d,J=6.6Hz),1.53-1.60(1H,m),2.55(1H,d,J=6.7 Hz),3.56(1H,d,J=16.7Hz),3.86(3H,s),4.02(1H,d,J=9.7 Hz),6.75(1H,d,J=8.6 Hz),7. 17-7.94(6H,m)FAB-MS(m/e):462[M+H]⁺

Example 3065

[0936] (R¹:H;R²:H;R³:i-Pr;R⁴:H;R⁶:H;Z:Ph;R:4-MeO-3-Me-Ph)

[0937]¹HNMR(CDCl₃) δ:0.88(3H,d,J=6.7 Hz),1.09(3H,d,J=6.7Hz),1.39-1.62(1H,m),2.15(3H,s),2.51(1H,d,J=17.3 Hz),3.60(1H,d,J=17.3Hz),3.80(3H,s),4.00(1H,d,J=9.7 Hz),6.74(1H,d,J=8.6 Hz),7.01(1H,d,J=2.6Hz),7.10-7.21 (2H,m),7.44-7.53(2H,m),7.90-7.93(1H,m)FAB-MS(m/e):350[M+H]⁺

Example 3072

[0938] (R¹:H;R²:H;R¹:i-Pr;R⁴:H;R⁶:H;Z:Ph;R:3-I-4-MeNHCOCH₂O-Ph)

[0939] FAB-MS(m/e):519[M+H]⁺

Example 3073

[0940] (R¹:H;R²:H;R³:i-Pr;R⁴:H;R⁶:H;Z:Ph;R:4-EtNHCOCH₂O-3-I-Ph)

[0941] FAB-MS(m/e):533[M+H]⁺

Example 3074

[0942] (R¹:H;R²H;R³:i-Pr;R⁴:H;R⁶:H;Z:Ph;R:3-I-4-n-PrNHCOCH₂O-Ph)

[0943]¹HNMR(CDCl₃) δ:0.90(3H,d,J=6.6 Hz),0.96(3H,t,J=7.4Hz),1.11(3H,d,J=6.6 Hz),1.53-1.67(3H,m),2.57(1H,d,J=16.7Hz),3.35(2H,q,J=6.6 Hz),3.55(1H,d,J=16.7 Hz),4.03(1H,d, J=9.5Hz),4.49(2H,s),6.73(1H,d,J=8.6Hz),6.88-6.93(1H,m),7.16-7.19(1H,m),7.33(1H, dd, J=2.3,8.6Hz),7.48-7.57(2H,m),7.73(1H,d,J=2.3 Hz),7.92-7.95(1H,m)FAB-MS(m/e):547[M+H]⁺

Example 3082

[0944] (R¹:H;R²:H;R³:i-Pr;R⁴:H;R⁶:H;Z:Ph;R:4-cycloPrNHCOCH₂O-3-I-Ph)

[0945] FAB-MS(m/e):545[M+H]⁺

Example 3092

[0946] (R¹:H;R²:H;R³:i-Pr;R⁴:H;R⁶:H;Z:Ph;R:3-Cl-4-n-PrNHCOCH₂O-Ph)

[0947]¹HNMR(CDCl₃) δ:0.88(3H,d,J=6.6 Hz),0.94(3H,t,J=7.4Hz),1.11(3H,d,J=6.6 Hz),1.52-1.93(3H,m),2.58(1H,d,J=6.0Hz),3.32(2H,q,J=6.7 Hz),3.56(1H,d,J=16.0 Hz),4.03(1H,d, J=9.6 Hz),4.51(2H,s),6.74-6.79(1H,m),6.87(1H,d,J=8.6 Hz),7.16-7.19(1H,m),7.24(1H,dd,J=2.4,8.6 Hz),7.36(1H,d,J=2.4 Hz),7.48-7.57(2H,m),7.92-7.96(1H,m)FAB-MS(m/e):455/457[M+H]⁺

Example 3093

[0948] (R¹:H;R²:H;R³:i-Pr;R⁴:H;R⁶:H;Z:Ph;R:3-Br-4-n-PrNHCOCH₂O-Ph)

[0949]¹HNMR(CDCl₃) δ:0.89(3H,d,J=6.6 Hz),0.95(3H,t,J=7.4 Hz),1.11(3H,d,J=6.6 Hz),1.52-1.65(3H,m),2.58(1H,d,J=17.0 Hz),3.33(2H,q,J=6.6Hz),3.56(1H,d,J=17.0 Hz),4.03(1H,d, J=9.6Hz),4.50(2H,s),6.82-6.85(1H,m),6.83(1H,d,J=8.6Hz),7.16-7.19(1H,m),7.29-7.31(1H, m),7.48-7.57(3H,m),7.88-7.94(1H,m)FAB-MS(m/e):499/501[M+H]⁺

Example 3094

[0950] (R¹:H;R²:H;R³:i-Pr;R⁴:H;R⁶:H;Z:Ph;R:3-F-4-n-PrNHCOCH₂O-Ph)

[0951]¹HNMR(CDCl₃) δ:0.88(3H,d,J=6.6 Hz),0.92(3H,t,J=7.4Hz),1.11(3H,d,J=6.6 Hz),1.51-1.64(3H,m),2.58(1H,d,J=17.5Hz),3.30(2H,q,J=6.8 Hz),3.55(1H,d,J=17.5 Hz),4.03(1H,d, J=9.5 Hz),4.51(2H,s),6.61-6.64(1H,m),6.92(1H,t,J=8.5 Hz),7.04(1H,d,J=11.9Hz),7.07-7.18 (2H,m),7.48-7.57(2H,m),7.91-7.98(1H,m)FAB-MS(m/e):439[M+H]⁺

Example 3095

[0952] (R¹:H;R²:H;R³:i-Pr;R⁴:H;R⁶:H;Z:Ph;R:3-Me-4-n-PrNHCOCH₂O-Ph)

[0953]¹HNMR(CDCl₃) δ:0.87(3H,d,J=6.7 Hz),0.92(3H,t,J=7.4Hz),1.09(3H,d,J=6.7 Hz),1.49-1.59(3H,m),2.23(3H,s),2.54(1H,d,J=17.3Hz),3.21 (2H,q,J=6.7 Hz),3.58(1H,d,J=17.3 Hz),4.01(1H,d,J=9.6Hz),4.47(2H,s),6.49-6.51(1H,m),6.73(1H,d,J=8.6 Hz),7.08(1H,d, J=2.0Hz),7.14-7.18(2H,m),7.46-7.54(2H,m),7.90-7.93(1H,m)FAB-MS(m/e):435[M+H]⁺

Example 3096

[0954] (R¹:H;R²:H;R³:i-Pr;R⁴:H;R⁶:H;Z:Ph;R:4-EtNHCOCH₂O-3-F-Ph)

[0955] FAB-MS(m/e):425[M+H]⁺

Example 3103

[0956] (R¹:H;R²:H;R³:i-Pr;R⁴:H;R⁶:H;Z:Ph:R:3-F-4-HO-Ph)

[0957]¹HNMR(CDCl₃) δ:0.87(3H,d,J=6.7 Hz),1.11(3H,d,J=6.7Hz),1.54-1.66(1H,m),2.55(1H,d,J=17.3 Hz),3.54(1H,d,J=17.3Hz),4.02(1H,d,J=9.6Hz),5.38-5.41(1H,m),6.94-7.05(3H,m),7.16-7.19(1H,m),7.47-7.57(2H,m),7.91-7.94(1H,m)FAB-MS(m/e):340[M+H]⁺

Example 3104

[0958] (R¹:H;R^(2:)H;R³:i-Pr;R⁴:H;R⁶:H;Z:Ph;R:3-F4-MeO-Ph)

[0959] Diastereomer A

[0960]¹HNMR(CDCl₃) δ:0.85(3H,d,J=6.9 Hz),1.19(3H,d,J=6.9Hz),2.60(1H,d,J=16.0 Hz), 3.40(1H,d,J=16.0Hz),3.63-3.69(1H,m),3.78(1H,d,J=3.2 Hz),3.84(3H,s),6.89(1H,dd, J=7.3,8.5Hz),7.02(1H,d,J=2.3 Hz),7.09(1H,dd,J=2.3,7.3 Hz),7.36(1H,dd,J=1.1,6.2Hz), 7.37-7.56 (2H,m),7.89(1H,dd,J=1.9,6.9 Hz) FAB-MS(m/e):354[M+H]⁺

[0961] Diastereomer B

[0962]¹HNMR(CDCl₃) δ:0.87(3H,d,J=6.6 Hz),1.11(3H,d,J=6.6Hz),1.55-1.63(1H,m),2,55(1H,d,J=17.4 Hz),3.55(1H,d,J=17.4Hz),3.87(3H,s),4.02(1H,d,J=9.6 Hz),6.91(1H,t,J=8.5Hz),6.98(1H,dd,J=2.3,12.2 Hz),7.07(1H,ddd,J=1.1,2.3,8.5Hz),7.16-7.19(1H,m),7.48-7.56(2H,m),7.91-7.94(1H,m)FAB-MS(m/e):354[M+H]⁺

Example 3107

[0963] (R¹:H;R²:H;R³:i-Pr;R⁴:H;R⁶:H;Z:Ph;R:3,4-Cl₂-Ph)

[0964] FAB-MS(m/e):375[M+H]⁺

Example 3112

[0965] (R¹:H;R²:H;R³:i-Pr;R⁴:H;R⁶:H;Z:Ph;R:3,5-Me₂-Ph)

[0966] FAB-MS(m/e):334[M+H]⁺

Example 3115

[0967] (R¹:H;R²:H;R³:i-Pr;R⁴:H;R⁶:H;Z:Ph;R:3,5-I₂-4-MeO-Ph)

[0968] FAB-MS(m/e):588[M+H]⁺

Example 3117

[0969] (R¹:H;R²:H;R³:i-Pr;R⁴:H;R⁶:H;Z:Ph;R:2,4,6-Me₃-Ph)

[0970] FAB-MS(m/e):348[M+H]⁺

Example 3126

[0971] (R¹:6-F;R²:H;R³:i-Pr;R⁴:H;R⁶:H;Z:Ph;R:Ph)

[0972] FAB-MS(m/e):324[M+H]⁺

Example 3129

[0973] (R¹:9-F;R²:H;R³:i-Pr;R⁴:H;R⁶:H;Z:Ph;R:Ph)

[0974] FAB-MS(m/e):324[M+H]⁺

Example 3134

[0975] (R¹:7-NO₂;R²:H;R³:i-Pr;R⁴:H;R⁶:H;Z:Ph;R:Ph)

[0976] FAB-MS(m/e):351[M+H]⁺

Example 3226

[0977] (R¹:H;R²:H;R³:i-Pr;R⁴:H;R⁶:H;Z:Ph;R:4-n-PrNHCOCH₂CH₂O-Ph)

[0978] FAB-MS(m/e):435[M+H]⁺

Example 3246

[0979] (R¹:H;R²:H;R¹:i-Pr;R⁴:H;R⁶:H;Z:Ph;R:3-F-4-i-PrNHCOCH₂CH₂O-Ph)

[0980] FAB-MS(m/e):453[M+H]⁺

Example 3258

[0981] (R¹:H;R²:H;R³:i-Pr;R⁴:H;R⁶:H;Z:Ph;R:3-Cl-4-EtNHCOCH₂CH₂O-Ph)

[0982] FAB-MS(m/e):455[M+H]⁺

Example 3266

[0983](R¹:H;R²:H;R^(3 :1)-Pr;R¹:H;R¹:H;Z:Ph;R:3-Me-4-n-BuNHCOCH₂CH₂O-Ph)

[0984] FAB-MS(m/e):463[M+H]⁺

Example 3296

[0985] (R¹:H;R²:H;R³:Bu;R⁴:H;R⁶:H;Z:Ph;R:3-Me-4-MeNHCOCH₂O-Ph)

[0986] FAB-MS(m/e):421[M+H]⁺

Example 3307

[0987] (R¹:H;R²:H;R³:t-Bu;R⁴:H;R⁶:H;Z:Ph;R:3-Me-4-n-PrNHCOCH₂O-Ph)

[0988] FAB-MS(m/e):449[M+H]⁺

Example 3319

[0989] (R¹:H;R²:H;R³:i-Pr;R⁴:Me;R⁶:H;Z:Ph;R:3-Cl-4-cycloPrNHCOCH₂O-Ph)

[0990] FAB-MS(m/e):467[M+H]⁺

Example 3324

[0991](R¹:H;R²:H;R³:i-Pr;R⁴:H;R⁶:H;Z:2,3-Pyridyl;R:3-Me-4-MeNHCO-CH₂OPh)

[0992] FAB-MS(m/e):408[M+H]⁺

Example 3331

[0993](R¹:H;R²:H;R³:i-Pr;R⁴:H;R⁶:H;Z:3,4-Pyridyl;R:3-Cl-4-EtNHCOCH₂O-Ph)

[0994] FAB-MS(m/e):442[M+H]⁺

Example 3337

[0995] (R¹:H;R²:H;R³:i-Pr;R⁴:H;R⁶:H;Z:Ph;R:4-EtNHCOCH₂O-3-F-(2-Pyridyl))

[0996] FAB-MS(m/e):446[M+H]⁺

Example 3344

[0997] (R¹:H;R²:H;R³:i-Pr;R⁴:H;R⁶:H;Z:Ph;R:6-EtNHCOCH₂O-5-I-(3-Pyridyl))

[0998] FAB-MS(m/e):534[M+H]⁺

Example 3351

[0999] (R¹:H;R²:H;R³:i-Pr;R⁴:H;R⁶:H;Z:Ph;R:4-EtNHCOCH₂O-3-NO₂-Ph)

[1000] FAB-MS(m/e):452[M+H]⁺

Example 3412

[1001] (R¹:H;R²:H;R³:i-Pr;R⁴:H;R⁶:Me;Z:Ph;R:3-Cl-4-EtNHCOCH₂O-Ph)

[1002] FAB-MS(m/e):455[M+H]⁺

Example 3418

[1003] (R¹:H;R²:H;R³:i-Pr;R⁴:H;R⁶:Et;Z:Ph;R:4-EtNHCOCH₂O-3-Me-Ph)

[1004] FAB-MS(m/e):449[M+H]⁺

Example 3464

[1005](R¹:H;R²:H;R³:i-Pr;R¹:H;R⁶:H;Z:pyrimidin-4,5-yl;R:4-n-BuNHCO-CH₂OPh)

[1006] FAB-MS(m/e):437[M+H]⁺

Example 3472

[1007] (R¹:H;R²:H;R³:i-Pr;R⁴:H;R⁶:H;Z:Ph;R:3-Cl-4-HO-Ph)

[1008]¹HNMR(CDCl₃) δ:0.88(3H,d,J=6.7 Hz),1.11(3H,d,J=6.7Hz),1.53-1.65(1H,m),2.55(1H,d, J=17.5 Hz),3.54(1H,d,J=17.5Hz),4.01(1H,d,J=9.5 Hz),6.98(1H,d,J=8.6Hz),7.10-7.20(1H,m),7.13(1H,dd,J=2.3 ,8.6 Hz),7.27(1H,d,J=2.3Hz),7.47-7.57(2H,m),7.91-7.94(1H,m) FAB-MS(m/e):356[M+H]⁺

Example 3473

[1009] (R¹:H;R²:H;R³:i-Pr;R⁴:H;R⁶:H;Z:Ph;R:4-HO-3-Me-Ph)

[1010]¹HNMR(CDCl₃) δ:0.86(3H,d,J=6.6 Hz),1.08(3H,d,J=6.6 Hz),1.53-1.61(3H,m),2.20(3H, s),2.50(1H,d,J=17.3 Hz),3.60(1H,d,J=17.3Hz),4.00(1H,d,J=9.7 Hz),5.98(1H,s),6.76(1H, d,J=8.2 Hz),6.99(1H,d,J=8.2Hz),7.01(1H,s),7.18(1H,dd,J=1.5,6.4 Hz),7.44-7.54(2H,m), 7.91(1H,dd,J=1.5,6.2 Hz) FAB-MS(m/e):336[M+H]⁺

Example 3474

[1011] (R¹:H;R²:H;R³:i-Pr;R⁴:H;R⁶:H;Z:Ph;R:4-HO₂CCH₂O-3-Me-Ph)

[1012]¹HNMR(CDCl₃) δ:0.86(3H,d,J=6.6 Hz),1.07(3H,d,J=6.6Hz),1.47-1.59(1H,m),2.19(3H,s),2.52(1H,d,J=17.3 Hz),3.58(1H,d,J=17.3Hz),4.00(1H,d,J=9.8 Hz),4.60(2H,s),5.99-6.13(1H, m),6.63(1H,d,J=8.3Hz),7.05-7.17(3H,m),7.44-7.52(2H,m),7.90-7.93(1H,m)FAB-MS(m/e):394[M+H]⁺

Example 3475

[1013] (R¹:H;R^(2:)H;R³:i-Pr;R⁴:H;R⁶:H;Z:Ph;R:3,5-Cl₂-4-n-PrNHCOCH₂O-Ph)

[1014]¹HNMR(CDCl₃) δ:0.94(3H,d,J=6.4 Hz),0.98(3H,t,J=7.5Hz),1.13(3H,d,J=6.4 Hz),1.54-1.68(3H,m),2.63(1H,d,J=16.1Hz),3.35(2H,q,J=6.6 Hz),3.50(1H,d,J=16.1 Hz),4.04(1H,d, J=9.7 Hz),4.51(2H,s),6.93-6.94(1H,m),7.22-7.25(1H,m),7.33(2H,s),7.51-7.61(2H,m),7.92-7.95(1H,m)FAB-MS(m/e):489/491[M+H]⁺

Example 3476

[1015] (R¹:H;R²:H;R³:i-Pr;R⁴:H;R⁶:H;Z:Ph;R:3-Me-4-n-PrNHCSCH₂O-Ph)

[1016]¹HNMR(CDCl₃) δ:0.87(3H,d,J=6.6 Hz),0.95(3H,t,J=7.5Hz),1.09(3H,d,J=6.6 Hz),1.51-1.75(3H,m),2.23(3H,s),2.54(1H,d,J=17.4Hz),3.59(1H,d,J=17.4 Hz),3.71 (2H,q,J=6.6 Hz),4.01(1H,d,J=9.8Hz),4.88(2H,s),6.74(1H,d,J=8.2Hz),7.09(1H,d,J=2.2Hz),7.14-7.17(2H,m),7.46-7.54(2H,m),7.91-7.93(1H,m),8.19-8.21(1H,m)FAB-MS(m/e):451[M+H]⁺

Example 3477

[1017] (R¹:H;R²:i;R³:i-Pr;R⁴:H;R⁶:H;Z:Ph;R:3,5-Cl2-4-n-PrNHCSCH₂O-Ph)

[1018]¹HNMR(CDCl₃) δ:0.93(3H,d,J=6.8 Hz),1.04(3H,t,J=7.4Hz),1.13(3H,d,J=6.8 Hz),1.32-1.41(1H,m),1.72-1.81(2H,m),2.62(1H,d,J=17.7Hz),3.51(1H,d,J=17.7 Hz),3.75(2H,q, J=6.6 Hz),4.04(1H,d,J=9.7Hz),4.89(2H,s),7.22(1H,d,J=7.9 Hz),7.33(2H,s),7.52-7.69(2H,m),7.93-7.95(1H,m),8.69-8.71(1H,m) FAB-MS(m/e):505/507[M+H]⁺

Example 3478

[1019] (R¹:H;R^(2:)H;R³:i-Pr;R⁴:H;R⁶:H;Z:Ph;R:4-n-Pentyl-NHCOCH₂O-Ph)

[1020]¹HNMR(CDCl₃) δ:0.83-0.96(3H,m),0.87(3H,d,J=6.7 Hz),1.10(3H,d,J=6.7Hz),1.14-1.70(7H,m),2.56(1H,d,J=17.2 Hz),3.32(2H,q,J=6.6Hz),3.60(1H,d,J=17.2 Hz),4.02(1H,d, J=9.6Hz),4.46(2H,s),6.49(1H,s),6.87(2H,d,J=9.0Hz),7.15-7.20(1H,m),7.25-7.34(2H, m),7.48-7.54(2H,m),7.91-7.92(1H,m)FAB-MS(m/e):449[M+H]⁺

Example 3479

[1021] (R¹:H;R^(2:)H;R³:i-Pr;R⁴:H;R⁶:Me;Z:Ph;R:4-MeO-Ph)

[1022]¹HNMR(CDCl₃) δ:0.69(3H,d,J=7.5 Hz),0.91 (3H,d,J=6.7Hz),1.11(3H,d,J=6.7 Hz),1.48-1.73(1H,m),3.51(1H,q,J=7.5Hz),3.77(3H,s),4.02(1H,d,J=9.6 Hz),6.83(2H,d,J=8.9Hz),7.10-7.13(1H,m),7.24(2H,d,J=8.9 Hz),7.46-7.51(2H,m),7.89-7.99(1H,m)FAB-MS(m/e):350[M+H]⁺

Example 3480

[1023] (R¹:H;R¹:H;R³:i-Pr;R⁴:H;R⁶:Me;Z:Ph;R:4-HO-Ph)

[1024]¹HNMR(CDCl₃) δ:0.68(3H,d,J=7.5 Hz),0.89(3H,d,J=6.6Hz),1.10(3H,d,J=6.6 Hz),1.48-1.69(1H,m),3.52(1H,q,J=7.5Hz),4.02(1H,dd,J=1.0,9.5 Hz),5.63(1H,s),6.79(2H,d,J=8.8Hz),7.11-7.15(1H,m),7.18(2H,d,J=8.8 Hz),7.44-7.54(2H,m),7.90-7.92(1H,m)FAB-MS(m/e):336[M+H]⁺

Example 3481

[1025] (R¹:H;R²:H;R³:i-Pr;R⁴:H;R.:Me;Z:Ph;R:4-n-PrNHCOCH₂O-Ph)

[1026]¹HNMR(CDCl₃) δ:0.70(3H,d,J=7.6 Hz),0.90(3H,d,J=7.4Hz),0.90(3H,d,J=6.6 Hz),1.11(3H,d,J=6.6Hz),1.48-1.66(3H,m),3.30(2H,q,J=6.8 Hz),3.50(1H,q,J=7.5 Hz),4.04(1H,dd,J=1.0,9.5 Hz),4.46(2H,s),6.50-6.51(1H,m),6.86(2H,d,J=8.9Hz),7.09-7.12(1H,m),7.29(2H, d,J=8.9 Hz),7.46-7.52(2H,m),7.91-7.94(1H,m)FAB-MS(m/e):435[M+H]⁺

Example 3482

[1027] (R¹:H;R²:H;R³:i-Pr;R⁴:H;R⁶:Br;Z:Ph;R:4-n-PrNHCOCH₂O-Ph)

[1028]¹HNMR(CDCl₃) δ:0.90(3H,d,J=6.6 Hz),0.99(3H,t,J=6.6Hz),1.17(3H,d,J=6.6 Hz),1.51-1.74(3H,m),3.30(2H,q,J=6.7Hz),4.36(1H,d,J=9.5 Hz),4.47(2H,s),5.14(1H,s),6.47-6.50(1H,m),6.91(2H,d,J=8.9 Hz),7.16-7.19(1H,m),7.34(2H,d,J=8.9 Hz),7.50-7.57(2H,m),7.91-7.94(1H,m) FAB-MS(m/e):499/501[M+H]⁺

Example 3485

[1029](R¹:H;R²:l;R³:i-Pr;R⁴:H;R⁶:MeSO₂NHCH₂CH₂;Z:Ph;R:4-n-PrNHCO-CH₂O-Ph)

[1030] FAB-MS(m/e):542[M+H]⁺

Example 3486

[1031] (R¹:H;R²:H;R³:i-Pr;R⁴:H;R⁶:MeO₂CCH₂;Z:Ph;R:4-n-PrNHCOCH₂O-Ph)

[1032] FAB-MS(m/e):493[M+H]⁺

Example 3487

[1033] (R¹:H;R²:H;R³:i-Pr;R⁴:H;R⁶:HOCH₂CH₂;Z:Ph;R:4-n-PrNHCOCH₂O-Ph)

[1034] FAB-MS(m/e):465[M+H]⁺

Example 3488

[1035] (R¹:H;R²:H;R³:i-Pr;R⁴:H;R⁶:H;Z:Ph;R:3,5-Cl₂-4-n-PrNHCOCH₂O-Ph)

[1036]¹HNMR(CDCl₃) δ:0.98(3H,t,J=7.4 Hz),1.03(3H,d,J=6.6Hz),1.15(3H,d,J=6.6 Hz),1.52-1.67(3H,m),2.61(1H,d,J=18.0Hz),3.35(2H,q,J=6.6 Hz),3.55(1H,d,J=18.0 Hz),4.51(2H,s),4.57(1H,d,J=10.4Hz),6.89-6.93(1H,m),7.53-7.61(2H,m),8.12-8.15(1H,m)FAB-MS(m/e):505/507[M+H]⁺

Example 3489

[1037] (R¹:H;R^(2:)H;R³:i-Pr;R⁴:H;R⁶:H;Z:Ph;R:3,5-Cl₂-4-n-PrNHCSCH₂O-Ph)

[1038]¹HNMR(CDCl₃) δ:1.02(3H,d,J=6.3 Hz),1.04(3H,t,J=7.4Hz),1.14(3H,d,J=6.3 Hz),1.52-1.59(1H,m),1.71-1.83(2H,m),2.61(1H,d,J=17.5 Hz),3.56(1H,d,J=17.5 Hz),3.75(2H,q, J=6.6Hz),4.56(1H,d,J=10.3Hz),4.90(2H,s),7.17-7.20(1H,m),7.23(2H,s),7.53-7.60(2H,m),8.12-8.15(1H,m) FAB-MS(m/e):521/523/525[M+H]⁺

Example 3492

[1039] (R¹:H;RH;R³:i-Pr;R⁴:H;R⁶:H;Z:pyrimidin-4,5-yl;R:4-n-BuNHCO-CH₂OPh)

[1040] FAB-MS(m/e):453[M+H]⁺

Example 3499

[1041](R¹:H;R²:H;R³:i-Pr;R⁴:H;R⁵:MeO;R⁶:H;Z:Ph;R:3-Me-4-n-PrNHCO-CH₂O-Ph)

[1042] Geometrical Isomer A

[1043]¹HNMR(CDCl₃) δ:0.92(3H,t,J=7.5 Hz),0.93(3H,d,J=6.6Hz),1.06(3H,d,J=6.6 Hz),1.46-1.71 (3H,m),2.22(3H,s),2.63(1H,d,J=18.1Hz),3.31(2H,q,J=6.7 Hz),3.88(3H,s),3.93(1H, dd,J=1.0,18.1Hz),4.38(1H,d,J=9.9 Hz),4.47(2H,s),6.50-6.52(1H,m),6.72(1H,d, J=8.5Hz),7.11 (1H,d,J=2.4 Hz),7.11-7.13(1H,m),7.21(1H,dd,J=2.4,8.5Hz),7.39-7.49(2H,m),7.81-7.84(1H,m) FAB-MS(m/e):464[M+H]⁺

[1044] Geometrical Isomer B

[1045]¹HNMR(CDCl₃) δ:0.59(3H,d,J=6.8 Hz),0.92(3H,t,J=7.4Hz),0.97(3H,d,J=6.8Hz),1.52-1.61(2H,m),2.04-2.12(1H,m),2.23(3H,s),2.90(1H,d,J=17.3Hz),3.29(2H,q,J=6.7 Hz), 3.71(1H,dd,J=1.5,17.3Hz),3.79(3H,s),4.46(2H,s),4.91 (1H,dd,J=1.2,7.6Hz),6.50-6.51(1H,m),6.73(1H,d,J=8.5 Hz),7.11-7.13(1H,m),7.14(1H,d,J=2.4Hz),7.23(1H,dd,J=2.4, 8.5 Hz),7.37-7.50(2H,m),7.79-7.82(1H,m)FAB-MS(m/e):464[M+H]⁺

Example 3500

[1046] (R¹:H;R²:H;R³:i-Pr;R⁴:H;R⁵:HO;R⁶:H;Z:Ph;R:3-Cl-4-n-PrNHCOCH₂O-Ph)

[1047] FAB-MS(m/e):470[M+H]⁺

Example 3501

[1048] (R¹:H;R²:H;R³:i-Pr;R⁴:H;R⁵:Me:R⁶::H;Z:Ph;R:4-n-PrNHCOCH₂O-Ph)

[1049] FAB-MS(m/e):434[M+H]⁺

Example 3509

[1050] (R¹:H;R²:H;R³:i-Pr;R⁴:H;R⁶:Me;R⁷:Me;Z:Ph;R:4-MeO-Ph)

[1051]¹HNMR(CDCl₃) δ:0.52(3H,s),1.01 (3H,d,J=6.6 Hz),1.29(3H,d,J=6.6Hz),1.44(3H,s), 1.85-1.99(1H,m),3.77(3H,s),4.01(1H,d,J=10.3Hz),6.78(2H,d,J=9.1 Hz),7.14(2H,d, J=9.1Hz),7.47-7.66(3H,m),7.92-7.95(1H,m) FAB-MS(m/e):364[M+H]⁺

Example 3510

[1052] (R¹:H;R²:H;R³:i-Pr;R⁴:H;R⁶:Me;R⁷:Me;Z:Ph;R:4-HO-Ph)

[1053]¹HNMR(CDCl₃) δ:0.50(3H,s),0.97(3H,d,J=6.6 Hz),1.28(3H,d,J=6.6Hz),1.44(3H,s), 1.83-1.91(1H,m),4.01(1H,d,J=10.3Hz),5.91-5.92(1H,m),6.74(2H,d,J=8.9 Hz),7.04(2H,d, J=8.9Hz),7.47(1H,d,J=7.5 Hz),7.93(1H,d,J=7.5 Hz) FAB-MS(m/e):350[M+H]⁺

Example 3511

[1054] (R¹:H;R²:H;R³:i-Pr;R⁴:H;R⁶:Me;R⁷:Me;Z:Ph;R:4-n-PrNHCOCH₂O-Ph)

[1055]¹HNMR(CDCl₃) δ:0.50(3H,s),0.90(3H,t,J=7.4 Hz),1.02(3H,d,J=6.5Hz),1.30(3H,d, J=6.5Hz),1.43(3H,s),1.51-1.58(2H,m),1.85-1.89(1H,m),3.29(2H,q,J=6.8Hz),4.02(1H,d, J=10.4 Hz),4.45(2H,s),6.49-6.50(1H,m),6.82(2H,d,J=9.0Hz),7.20(2H,d,J=9.0 Hz),7.47-7.67(3H,m),7.93-7.95(1H,m)FAB-MS(rm/e):449[M+H]hu +

Example 3515

[1056] (R¹:H;R²::H;R³:i-Pr;R⁴:H;R⁶:MeCOCH₂;R⁷:Me;Z:Ph;R:4-n-PrNHCOCH₂O-Ph)

[1057] FAB-MS(m/e):491[M+H]⁺

Example 3516

[1058](R¹:H;R²:H;R³:i-Pr;R⁴:H;R⁶:MeO₂CCH₂;R⁷:Me;Z:Ph;R:4-n-PrNHCOCH₂O-Ph)FAB-MS(m/e):507[M+H]⁺

Example 4002

[1059]3-(1-Methylethyl)-9b-phenyl[1,3]thiazolo[2,3-a]isoindole-2,5(3H,9bH)-dione(compound of R¹:H;R²:H;R³:i-Pr;R⁴:H;Z:Ph;R:Ph in the general formula[I-4])

[1060] 1-Hydroxybenzotriazole hydrate (3.6 g, 26.5 mmol) and1-(3-dimethylamino-propyl)-3-ethylcarbodiimide hydrochloride (5.1 g,26.5 mmol) were added to a solution of 2-benzoylbenzoic acid (5.0 g,22.1 mmol), D-valine methyl ester hydrochloride (4.1 g, 24.3 mmol) andtriethylamine (9.2 ml, 66.3 mmol) in methylene chloride (250 ml) underice cooling, and the reaction mixture was stirred at room temperaturefor 3 hours. Aqueous saturated ammonium chloride solution was added tothe reaction mixture, and the mixture was extracted with chloroform. Theorganic layer was washed with aqueous saturated sodium chloridesolution, dried and concentrated under reduced pressure. The resultingresidue was purified by silica gel column chromatography (hexane:ethylacetate=1:1) to obtain a condensed product (4.9 g, yield: 65%). Sodiumhydrosulfide n hydrate (140 mg, 2.50 mmol) was added to a solution ofthe obtained condensed product (212 mg, 0.62 mmol) in tetrahydrofuran(4.5 ml), the reaction mixture was stirred at room temperature for 12hours, and aqueous 1N hydrochloric acid solution was added to thereaction mixture at room temperature. The mixture was extracted withethyl acetate, the organic layer was dried and concentrated underreduced pressure, and the obtained unpurified thiocarboxylic acid wasdissolved in methylene chloride (2.5 ml). Trifluoroacetic acid (2.5 ml)was added to the reaction mixture at room temperature, and the mixturewas stirred at room temperature for 30 minutes and concentrated underreduced pressure. The resulting residue was subjected three times toazeotropic distillation with toluene, and the mixture was concentratedunder reduced pressure. The residue was purified by silica gel columnchromatography (hexane:ethyl acetate=2:1) to obtain the diastereomer Aof the captioned compound (43.0 mg, yield: 21%) as colorless oily matterand the diastereomer B thereof (7.0 mg, yield: 4%) as colorless oilymatter.

[1061] Diastereomer A

[1062]¹HNMR(CDCl₃) δ:1.14(3H,d,J=6.7 Hz),1.31(3H,d,J=6.7 Hz),3.61-3.71(1H,m),3.81(1H, dd,J=0.7,4.6 Hz),7.31-7.60(8H,m),7.91(1H,dd,J=2.7,7.9Hz) FAB-MS(m/e):324[M+H]⁺

[1063] Diastereomer B

[1064]¹HNMR(CDCl₃) δ:0.85(3H,d,J=6.6 Hz), 1.05(3H,d,J=6.6 Hz),1.51-1.62(1H,m),4.53(1H, d, J=10.3 Hz),7.14-7.17(1H,m),7.30-7.98(8H,m)FAB-MS(m/e):324[M+H]⁺

[1065] In the same manner as in Example 4002, compounds of Examples4007, 4011, 4024, 4061, 4063, 4073, 4074, 4079, 4087, 4092, 4113, 4410,4419 and 4424 corresponding to the compound numbers of the compounds ofthe general formula [I-4] in the aforementioned compound lists wereobtained. Physical constants of these compounds are shown below.

Example 4007

[1066] (R¹:H;R²:H;R³:i-Pr;R⁴:H;Z:Ph;R:4-HO-Ph)

[1067]¹HNMR(CDCl₃) δ:0.85(3H,d₄J=6.6 Hz),1.07(3H,d,J=6.7Hz),1.52-1.64(1H,m),4.50(1H,d,J=10.4 Hz),5.11(1H,brs),6.79(2H,d,J=8.8Hz),7.15-7.17(1H,m),7.32(2H,d, J=8.8 Hz),7.51-7.57(2H,m),7.94-7.97(1H,m)FAB-MS(m/e):340[M+H]⁺

Example 4011

[1068] (R¹:H;R²:H;R³:i-Pr;R⁴:H;Z:Ph;R:4-MeO-Ph)

[1069]¹HNMR(CDCl₃) δ:0.85(3H,d,J=6.1 Hz),1.07(3H,d,J=6.7Hz),1.52-1.64(1H,m),3.81(3H, s),4.50(1H,d,J=10.4 Hz),6.85(2H,d,J=9.0Hz),7.14-7.17(1H,m),7.36(2H,d,J=90 Hz), 7.51-7.57(2H,m),7.94-7.97(1H,m)FAB-MS(m/e):354[M+H]⁺

Example 4024

[1070] (R¹:H;R² :H;R³:i-Pr;R⁴:H;Z:Ph;R:4-n-PrNHCOCH₂O-Ph)

[1071]¹HNMR(CDCl₃) δ:0.84(3H,d,J=6.6 Hz),0.91 (3H,t,J=7.4Hz),1.07(3H,d,J=6.7 Hz),1.50-1.62(3H,m),3.31(2H,q,J=7.0Hz),4.48(2H,s),4.51(1H,d,J=10.4 Hz),6.54(1H,brs),6.89(2H,d,J=9.0Hz),7.13-7.16(1H,m),7.41(2H,d,J=9.0 Hz),7.52-7.59(2H,m),7.95-7.98(1H,m)FAB-MS(m/e):439[M+H]⁺

Example 4061

[1072] (R¹:H;R²:H;R³:i-Pr;R⁴:H;Z:Ph;R:4-HO-3-I-Ph)

[1073]¹HNMR(CDCl₃) δ:0.89(3H,d,J=6.6 Hz),1.08(3H,d,J=6.8Hz),1.52-1.64(1H,m),4.50(1H,d,J=10.4 Hz),5.70(1H,brs),6.94(1H,d,J=8.6Hz),7.14-7.19(1H,m),7.30(1H,dd,J=2.4, 8.6Hz),7.53-7.62(2H,m),7.77(1H,d,J=2.4 Hz),7.95-7.98(1H,m)FAB-MS(m/e):466[M+H]⁺

Example 4063

[1074] (R¹:H;R²:H;R³:i-Pr;R⁴:H;Z:Ph;R:3-I-4-MeO-Ph)

[1075]¹HNMR(CDCl₃) δ:0.89(3H,d,J=6.6 Hz),1.08(3H,d,J=6.9Hz),1.52-1.64(1H,m),3.88(3H,s),4.51(1H,d,J=10.4 Hz),6.76(1H,d,J=8.6Hz),7.16-7.18(1H,m),7.43(1H,dd,J=2.5, 8.6Hz),7.55-7.59(2H,m),7.81(1H,d,J=2.5 Hz),7.95-7.98(1H,m)FAB-MS(m/e):480[M+H]⁺

Example 4073

[1076] (R¹:H;R²:H;R³:i-Pr;R⁴:H;Z:Ph;R:4-EtNHCOCH₂O-3-I-Ph)

[1077]¹HNMR(CDCl₃) δ:0.89(3H,d,J=6.6 Hz),1.08(3H,d,J=6.6Hz),1.23(3H,t,J=7.2Hz),1.50-1.58(1H,m),3.38-3.47(2H,m),4.45(2H,s),4.52(1H,d,J=10.7Hz),6.73(1H,d,J=8.5 Hz),6.86(1,brs),7.14-7.26(1H,m),7.47(1H,dd,J=2.2,8.5Hz),7.56-7.59(2H,m),7.84(1H,d, J=2.2 Hz),7.96-7.99(1H,m)FAB-MS(m/e):551[M+H]⁺

Example 4074

[1078] (R¹:H;R²:H;R³:i-Pr;R⁴:H;Z:Ph;R:3-I-4-n-PrNHCOCH₂O-Ph)

[1079]¹HNMR(CDCl₃) δ:0.89(3H,d,J=6.6 Hz),0.98(3H,t,J=7.4Hz),1.08(3H,d,J=6.6 Hz),1.50-1.65(3H,m),3.36(2H,q,J=7.0 Hz),4.51(2H,s),4.52(1H,d,J=10.4 Hz),6.74(1H,d,J=8.6 Hz), 6.91(1H,brs),7.14-7.17(1H,m),7.48(1H,dd,J=2.4,8.6Hz),7.56-7.60(2H,m),7.85(1H,d, J=2.4 Hz),7.96-7.99(1H,m)FAB-MS(m/e):565[M+H]⁺

Example 4079

[1080] (R¹:H;R²:H;R³:i-Pr;R⁴:H;Z:Ph;R:4-t-BuO₂CCH₂O-3-I-Ph)

[1081]¹HNMR(CDCl₃) δ:0.88(3H,d,J=6.6 Hz),1.07(3H,d,J=6.6Hz),1.46(9H,s),1.52-1.64(1H, m),4.50(1H,d,J=10.5Hz),4.57(2H,s),6.62(1H,d,J=8.7 Hz),7.15-7.18(1H,m),7.40(1H,dd, J=2.4,8.7Hz),7.55-7.59(2H,m),7.84(1H,d,J=2.4 Hz),7.95-7.98(1H,m)FAB-MS(m/e):580[M+H]⁺

Example 4087

[1082] (R¹:H;R²:H;R³:i-Pr;R⁴:H;Z:Ph;R:4-HO2CCH₂O-3-I-Ph)

[1083]¹HNMR(CDCl₃) δ:0.88(3H,d,J=6.0 Hz),1.07(3H,d,J=6.6Hz),1.50-1.58(1H,m),4.51(1H, d,J=10.6Hz),4.73(2H,s),5.93(1H,brs),6.69(1H,d,J=8.5Hz),7.16-7.19(1H,m),7.42(1H,dd, J=2.2,8.5 Hz),7.54-7.61(2H,m),7.85(1H,d,J=2.2 Hz),7.96-7.99(1H,m) FAB-MS(m/e):524[M+H]⁺

Example 4092

[1084] (R¹:H;R^(2:)H;R¹:i-Pr;R⁴:H;Z:Ph;R:3-Cl-4-n-PrNHCOCH₂O-Ph)

[1085]¹HNMR(CDCl₃) δ:0.88(3H,d,J=6.6 Hz),0.95(3H,t,J=7.4Hz),1.08(3H,d,J=6.7 Hz),1.50-1.65(3H,m),3.34(2H,q,J=6.9Hz),4.52(1H,d,J=10.3 Hz),4.53(2H,s),6.78(1H,brs),6.88(1H,d,J=8.6Hz),7.14-7.17(1H,m),7.39(1H,dd,J=2.4,8.6 Hz),7.50(1H,d,J=2.4Hz),7.56-7.62(2H,m),7.96-7.99(1H,m) FAB-MS(m/e):473[M+H]⁺

Example 4113

[1086] (R¹:H;Re:H;R³:i-Pr;R⁴:H;Z:Ph;R:3,5-I₂-4-HO-Ph)

[1087]¹HNMR(CDCl₃) δ:0.93(3H,d,J=6.6 Hz),1.10(3H,d,J=6.6Hz),1.52-1.64(1H,m),4.51(1H,d, J=10.6Hz),7.18-7.21(1H,m),7.57-7.62(2H,m),7.75(2H,s),7.96-7.99(1H,m)FAB-MS(m/e):592[M+H]⁺

Example 4410

[1088] (R¹:H;R²:H;R³:i-Pr;R⁴:H;Z:4,5-pyridazinyl;R:4-n-PrNHCOCH₂O-Ph)

[1089] FAB-MS(m/e):441[M+H]⁺

Example 4419

[1090] (R¹:H;R²:H;R³:i-Pr;R⁴:H;Z:Ph;R:4-n-PrNHCOCH₂O-pyrazin-2-yl)

[1091] FAB-MS(m/e):441[M+H]⁺

Example 4424

[1092] (R¹:H;R²:H;R³:i-Pr;R⁴:H;Z:Ph;R:3-Cl-4-HO-Ph)

[1093]¹HNMR(CDCl₃) δ:0.88(3H,d,J=6.6 Hz),1.08(3H,d,J=6.6Hz),1.52-1.64(1H,m),4.51 (1H,d,J=10.3 Hz),5.72(1H,brs),6.98(1H,d,J=8.6Hz),7.16-7.19(1H,m),7.24(1H,dd,J=2.2, 8.6 Hz),7.47(1H,d,J=2.2Hz),7.56-7.59(2H,m),7.95-7.98(1H,m) FAB-MS(m/e):374[M+H]⁺

Pharmaceutical Preparation Example 1

[1094] Compound of Example 1002 (45 parts), heavy magnesium oxide (15parts) and lactose (75 parts) are uniformly mixed to form powdery orfinely granular powder of 350 μm or less. This powder is put in capsulevessels to obtain capsules.

Pharmaceutical Preparation Example 2

[1095] Compound of Example 3011 (45 parts), starch (15 parts), lactose(16 parts). crystalline cellulose (21 parts), polyvinyl alcohol (3parts) and distilled water (30 parts) are uniformly mixed, disrupted andgranulated, dried, and then sieved to obtain granules of 141 to 177 μm.

Pharmaceutical Preparation Example 3

[1096] After granules are obtained in the same manner as inPharmaceutical preparation example 2, calcium stearate (4 parts) isadded to these granules (96 parts), and the mixture is compressionmolded to obtain tablets of diameter 10 mm.

Pharmaceutical Preparation Example 4

[1097] After granules are obtained in the same manner as inPharmaceutical preparation example 2, crystalline cellulose (10 parts)and calcium stearate (3 parts) are added to these granules (90 parts),the mixture is compression molded to obtain tablets of diameter 8 mm,and a suspension obtained by mixing syrup gelatin and precipitatedcalcium carbonate is added to these tablets to obtain sugar-coatedtablets.

[1098] Industrial Applicability

[1099] The compounds of the invention show an activity to bring abouthigh GLP-1 concentration in the blood, and can be used as agents fortreating diabetes, prophylactic agents for chronic complications ofdiabetes or drugs against obesity.

1. A compound represented by the general formula [I] or apharmaceutically acceptable salt thereof;

wherein, R represents (1) an aryl group, (2) a mono- to tricyclic C₇-C₁₅aromatic carbocyclic group selected from the group consisting ofacenaphthylenyl, adamantyl, anthryl, indenyl, norbornyl and phenanthryl,(3) a 5- or 6-membered heterocyclic group selected from the groupconsisting of isoxazolyl, isothiazolyl, imidazolyl, oxazolyl,oxadiazolyl, thiazolyl, thiadiazolyl, thienyl, triazinyl, triazolyl,pyridyl, pyrazinyl, pyrimidinyl, pyridazinyl, pyrazolyl, pyrrolyl,pyranyl, furyl, furazanyl, imidazolidinyl, imidazolinyl,tetrahydrofuranyl, pyrazolidinyl, pyrazolinyl, piperazinyl, piperidinyl,pyrrolidinyl, pyrrolinyl and morpholino (hereinafter, “isoxazolyl, . . .and morpholino” is referred to as a series of groups a), or (4) a mono-to tricyclic aromatic heterocyclic group having per one ring 1 to 5hetero atoms selected from the group consisting of nitrogen atoms,oxygen atoms and sulfur atoms, selected from the group consisting ofacridinyl, isoquinolyl, isoindolyl: indazolyl, indolyl, indolizinyl,ethylenedioxyphenyl, carbazolyl, quinazolinyl, quinoxalinyl,quinolidinyl, quinolyl, cumaronyl, chromenyl, phenanthridinyl,phenanthrolinyl, dibenzofuranyl, dibenzothiophenyl, cinnolinyl,thionaphthenyl, naphthyridinyl, phenazinyl, phenoxazinyl,phenothiazinyl, phthalazinyl, pteridinyl, purinyl, benzimidazolyl,benzoxazoly0001, benzothiazolyl, benzotriazolyl, benzofuranyl andmethylenedioxyphenyl (hereinafter, “acridinyl . . . andmethylenedioxyphenyl” is referred to as a series of groups B), each ofthe above-mentioned groups (1) to (4) may optionally have one or moresubstituents selected from the group consisting of (5) substituentsselected from the group consisting of azido, amino, carbamoyl,carbamoylamino, carbamoyloxy, carboxyl, cyano, sulfamoyl, sulfo, nitro,halogen, hydroxy, formyl, formylamino, cyclic saturated C₃-C₉ aliphaticgroups, cyclic unsaturated C₃-C₉ aliphatic groups, aralkyl,N-aralkylamino, N,N-diaralkylamino, aralkyloxy, aralkylcarbonyl,N-aralkylcarbamoyl, aryl, N-arylamino, N,N-diarylamino, aryloxy,arylsulfonyl, arylsulfonyloxy, N-arylsulfonylamino, N-arylsulfonylaminoC₁-C₁₀ alkylamino, N-arylsulfonylamino C₁-C₁₀ alkylcarbamoyl,N-arylsulfonylamino C₁-C₆ alkoxycarbonyl, arylsulfamoyl,arylsulfamoyloxy, N-arylsulfamoyl C₁-C₁₀ alkylcarbamoyl, arylsulfamoylC₁-C₆ alkoxycarbonyl, N-arylcarbamoyl, aroyl, aroxy, N-(N-aroylamino)C₁-C₁₀ alkylcarbamoyl, N-aroylamino C₁-C₁₀ alkoxycarbonyl, C₂-C₆alkanoyl, N—C₂-C₆ alkanoylamino, N,N-di-C₂-C₆ alkanoylamino, N—C₁-C₆alkylamino, N,N-di-C₁-C₆ alkylamino, N—C₁-C₁₀ alkylcarbamoyl, N—C₁-C₁₀alkylthiocarbamoyl, N,N-di-C₁-C₁₀ alkylcarbamoyl, N,N-di-C₁-C₁₀alkylthiocarbamoyl, N—C₂-C₆ alkenylcarbamoyl, N,N-di-C₂-C₆alkenylcarbamoyl, N-amino C₁-C₁₀ alkylcarbamoyl, N—C₁-C₆ alkoxy C₁-C₁₀alkylcarbamoyl, N—C₁-C₆ alkoxycarbonyl C₁-C₁₀ alkylcarbamoyl, N—C₁-C₆alkoxycarbonylamino C₁-C₁₀ alkylcarbamoyl, N—C₁-C₆ alkoxycarbonylaminoC₁-C₆ alkoxycarbonyl, C₁-C₆ alkylthio, N—C₁-C₆ alkylsulfamoyl,N,N-di-C₁-C₆ alkylsulfamoyl, C₁-C₆ alkylsulfinyl, C₁-C₆ alkylsulfonyl,N—C₁-C₆ alkylsulfonylamino, C₁-C₆ alkoxy, C₁-C₆ alkoxycarbonyl, aminoC₁-C₆ alkoxycarbonyl. N—C₃-C₆ cycloalkylamino, N,N-di-C₃-C₆cycloalkylamino, C₃-C₆ cycloalkyloxy, N—C₃-C₆ cycloalkylcarbamoyl andN,N-di-C₃-C₆ cycloalkylcarbamoyl, (6) 5- or 6-membered heterocyclicgroups selected from the group consisting of the above-mentioned seriesof groups A. (7) monocyclic to tricyclic aromatic heterocyclic groupshaving per one ring 1 to 5 hetero atoms selected from the groupconsisting of nitrogen atoms, oxygen atoms and sulfur atoms, selectedfrom the group consisting of the above-mentioned series of groups B, (8)substituents selected from the group consisting of N—C₁-C₁₀alkylcarbamoyl groups, N—C₁-C₁₀ alkylthiocarbamoyl groups, thiocarbonylgroups and carbonyl groups, each substituted with the above-mentionedheterocyclic group or the above-mentioned aromatic heterocyclic group,and (9) substituents selected from the group consisting ofstraight-chain saturated C₁-C₉ aliphatic groups, straight-chainunsaturated C₁-C₉ aliphatic groups, branched saturated C₁-C₉ aliphaticgroups, branched unsaturated C₁-C₉ aliphatic groups, C₁-C₆ alkoxygroups, C₁-C₆ alkylthio groups and N—C₁-C₆ alkylamino groups, each ofwhich groups may be substituted with the above-mentioned substituent,(hereinafter, the above-mentioned groups (5) to (9) are referred to asseries of groups C), R¹ and R² are the same or different, and represent(1) groups selected from the group consisting of hydrogen, azido, amino,carbamoyl, carbamoylamino, carbamoyloxy, carboxyl, cyano, sulfamoyl,sulfo, nitro, halogen, hydroxy, formyl, formylamino, cyclic saturatedC₃-C₉ aliphatic groups, cyclic unsaturated C₃-C₉ aliphatic groups,aralkyl, N-aralkylamino, aralkyloxy, aralkylcarbonyl, aryl, N-arylamino,aryloxy, arylsulfonyl, N-arylsulfonylamino, N-arylsulfonylamino C₁-C₁₀alkylamino, N-arylsulfonylamino C₁-C₁₀ alkylcarbamoyl,N-arylsulfonylamino C₁-C₆ alkoxycarbonyl, C₂-C₆ alkanoyl, N—C₂-C₆alkanoylamino, aroyl, N-aroylamino, N-aroyl C₁-C₁₀ alkylamino, N-aroylC₁-C₁₀ alkylcarbamoyl, N-C₁-C₆ alkylamino, N,N-di-C₁-C₆ alkylamino,N—C₁-C₁₀ alkylcarbamoyl, N,N-di-C₁-C₁₀ alkylcarbamoyl, N—C₁-C₆alkylsulfamoyl, C₁-C₆ alkylsulfinyl, C₁-C₆ alkylsulfonyl, N—C₁-C₆alkylsulfonylamino, C₁-C₆ alkylthio, C₁-C₆ alkoxy, C₁-C₆ alkoxycarbonyl,N-C₃-C₆ cycloalkylamino, C₃-C₆ cycloalkyloxy and N—C₃-C₆cycloalkylcarbamoyl (hereinafter, “hydrogen, . . . and N—C₃-C₆cycloalkylcarbamoyl” is referred to as a series of groups D), or (2)straight-chain saturated C₁-C₉ aliphatic groups, straight-chainunsaturated C₁-C₉ aliphatic groups, branched saturated C₁-C₉ aliphaticgroups or branched unsaturated C₁-C₉ aliphatic groups, N—C₁-C₆alkylamino groups, C₁-C₆ alkylthio groups or C₁-C₆ alkoxy groups, eachof which groups may optionally be substituted with the above-mentionedgroup, R³ and R⁴ are the same or different, and represent (1) groupsselected from the group consisting of hydrogen, azido, amidino, amino,carbamoyl, carbamoylamino, carbamoyloxy, carboxyl, guanidino, cyano,sulfamoyl, sulfo, nitro, halogen, hydroxy, formyl, formylamino, cyclicsaturated C₃-C₉ aliphatic groups, cyclic unsaturated C₃-C₉ aliphaticgroups, C₂-C₆ alkanoyl, N—C₂-C₆ alkanoylamino, N—C₁-C₆ alkylamino,N,N-di-C₁-C₆ alkylamino, N—C₁-C₁₀ alkylcarbamoyl, N,N-di-C₁-C₁₀alkylcarbamoyl, C₁-C₆ alkylthio, N—C₁-C₆ alkylsulfamoyl, C₁-C₆alkylsulfinyl, C₁-C₆ alkylsulfonyl, N—C₁-C₆ alkylsulfonylamino, C₁-C₆alkoxy, C₁-C₆ alkoxycarbonyl, N—C₃-C₆ cycloalkylamino, C₃-C₆cycloalkyloxy and N—C₃-C₆ cycloalkylcarbamoyl (hereinafter, “hydrogen, .. . and N—C₃-C₆ cycloalkylcarbamoyl” is referred to as a series ofgroups E), (2) groups selected from the group consisting ofstraight-chain saturated C₁-C₉ aliphatic groups, straight-chainunsaturated C₁-C₉ aliphatic groups, branched saturated C₁-C₉ aliphaticgroups and branched unsaturated C₁-C₉ aliphatic groups, each of whichgroups may optionally be substituted with the above-mentioned group, or(3) (3-1) aryl groups, (3-2) monocyclic to tricyclic C₇-C₁₅ aromaticcarbocyclic groups selected from the group consisting ofacenaphthylenyl, adamantyl, anthryl, indenyl, norbornyl and phenanthryl,(3-3) 5- or 6-membered heterocyclic groups selected from the groupconsisting of the aforementioned series of groups A, (3-4) monocyclic totricyclic aromatic heterocyclic groups having per one ring 1 to 5 heteroatoms selected from the group consisting of nitrogen atoms, oxygen atomsand sulfur atoms, selected from the group consisting of theaforementioned series of groups B, or (3-5) straight-chain saturatedC₁-C₉ aliphatic groups, straight-chain unsaturated C₁-C₉ aliphaticgroups, branched saturated C₁-C₉ aliphatic groups or branchedunsaturated C₁-C₉ aliphatic groups, each of which groups may optionallybe substituted with the above-mentioned aryl group, the above-mentionedaromatic carbocyclic group, the above-mentioned heterocyclic group orthe above-mentioned aromatic heterocyclic group, each of theabove-mentioned groups (3-1) to (3-5) being optionally substituted withone or more substituents selected from the group consisting of theaforementioned series of group C, or (4) R³ and R⁴ combine together toform a straight-chain saturated C₁-C₉ aliphatic group, a straight-chainunsaturated C₁-C₉ aliphatic group, a branched saturated C₁-C₉ aliphaticgroup, a branched unsaturated C₁-C₉ aliphatic group, a 5- or 6-memberedsaturated carbocyclic group, or a 5- or 6-membered unsaturatedcarbocyclic group, X¹ represents an oxygen atom, a sulfur atom or agroup NR⁵ (wherein R⁵ represents a group selected from the groupconsisting of hydrogen, halogen, hydroxy, N—C₁-C₆ alkylsulfonylamino,C₁-C₆ alkoxy, C₁-C₆ alkoxycarbonyl, C₂-C₆ alkanoyl, carbamoyl andN—C₁-C₁₀ alkylcarbamoyl; or a straight-chain saturated C₁-C₉ aliphaticgroup, a straight-chain unsaturated C₁-C₉ aliphatic group, a branchedsaturated C₁-C₉ aliphatic group or a branched unsaturated C₁-C₉aliphatic group, each of which groups may be substituted with theabove-mentioned group), X₂ represents an oxygen atom or a sulfur atom, Yrepresents an oxygen atom, a sulfur atom, a group NR⁵ or a group CR⁶R⁷(wherein R⁶ is a group selected from the group consisting of hydrogen,halogen, hydroxy, N—C₁-C₆ alkylsulfonylamino, C₁-C₆ alkoxy, C₁-C₆alkoxycarbonyl, C₂-C₆ alkanoyl, carbamoyl and N—C₁-C₁₀ alkylcarbamoyl;or a straight-chain saturated C₁-C₉ aliphatic group, a straight-chainunsaturated C₁-C₉ aliphatic group, a branched saturated C₁-C₉ aliphaticgroup or a branched unsaturated C₁-C₉ aliphatic group, each of whichgroups may optionally be substituted with the above-mentioned group, R7represents hydrogen or C₁-C₆ alkyl, and R⁵ is as defined above), and Zrepresents (1) a bi- or tricyclic saturated or unsaturated C₆-C₁₅condensed carbocyclic group selected from the group consisting ofcondensed aryl, acenaphthylenyl, adamantyl, anthryl, indanyl, indenyl,C₆-C₈ cycloalkanyl, C₆-C₈ cycloalkadienyl, C₆-C₈ cycloalkenyl,norbornyl, phenanthryl and fluorenyl, (2) a 6-membered heterocyclicgroup selected from the group consisting of isoquinolyl, isoindolyl,indazolyl, indolyl, indolizinyl, ethylenedioxyphenyl, quinazolinyl,quinoxalinyl, quinolidinyl, quinolyl, cumaronyl, chromenyl,thionaphthenyl, naphthyridinyl, pyridyl, pyrazinyl, pyrimidinyl,pyridazinyl, pyranyl, phthalazinyl, benzimidazolyl, benzoxazolyl,benzothiazolyl, benzotriazolyl, benzofuranyl and methylenedioxyphenyl,or (3) a bi- or tricyclic condensed aromatic heterocyclic group havingper one ring 1 to 5 hetero atoms selected from the group consisting ofnitrogen atoms, oxygen atoms and sulfur atoms.
 2. The compoundrepresented by the general formula [I-a] or pharmaceutically acceptablesalt thereof, according to claim 1;

wherein, R^(a) represents (1) an aryl group, (2) a mono- to tricyclicC₇-C₁₅ aromatic carbocyclic group selected from the group consisting ofadamantyl, anthryl, indenyl, norbornyl and phenanthryl, (3) a 5- or6-membered heterocyclic group selected from the group consisting ofisoxazolyl, isothiazolyl, imidazolyl, oxazolyl, oxadiazolyl, thiazolyl,thiadiazolyl, thienyl, triazolyl, pyridyl, pyrazinyl, pyrimidinyl,pyridazinyl, pyrazolyl, pyrrolyl, pyranyl, furyl, imidazolidinyl,imidazolinyl, tetrahydrofuranyl, pyrazolidinyl, pyrazolinyl,piperazinyl, piperidinyl, pyrrolidinyl, pyrrolinyl and morpholino(hereinafter, “isoxazolyl . . . and morpholino” is referred to as seriesof groups A′), or (4) a mono- to tricyclic aromatic heterocyclic grouphaving per one ring 1 to 5 hetero atoms selected from the groupconsisting of nitrogen atoms, oxygen atoms and sulfur atoms, selectedfrom the group consisting of isoquinolyl, isoindolyl, indazolyl,indolyl, ethylenedioxyphenyl, carbazolyl, quinazolinyl, quinoxalinyl,quinolidinyl, quinolyl, cumaronyl, chromenyl, phenanthridinyl,phenanthrolinyl, dibenzofuranyl, dibenzothiophenyl,cinnolinyl,thionaphthenyl, naphthyridinyl, phenazinyl, phenoxazinyl,benzimidazolyl, benzoxazolyl, benzothiazolyl, benzotriazolyl,benzofuranyl and methylenedioxyphenyl (hereinafter, “isoquinolyl . . .and methylenedioxyphenyl” is referred to as series of groups B′), eachof the above-mentioned groups (1) to (4) being optionally substitutedwith one or more substituents selected from the group consisting of (5)substituents selected from the group consisting of amino, carbamoyl,carbamoylamino, carbamoyloxy, carboxyl, nitro, halogen, hydroxy, cyclicsaturated C₃-C₉ aliphatic groups, cyclic unsaturated C₃-C₉ aliphaticgroups, aralkyl, N-aralkylamino, aralkyloxy, aralkylcarbonyl,N-aralkylcarbamoyl, aryl, N-arylamino, aryloxy, arylsulfonyl,arylsulfonyloxy, N-arylsulfonylamino, N-arylsulfonylamino C₁-C₁₀alkylamino, N-arylsulfonylamino C₁-C₁₀ alkylcarbamoyl,N-arylsulfonylamino C₁-C₆ alkoxycarbonyl, arylsulfamoyl,arylsulfamoyloxy, N-arylsulfamoyl C₁-C₁₀ alkylcarbamoyl, arylsulfamoylC₁-C₆ alkoxycarbonyl, N-arylcarbamoyl, aroyl, aroxy, N-(N-aroylamino)C₁-C₁₀ alkylcarbamoyl. N-aroylamino C₁-C₁₀ alkoxycarbonyl, C₂-C₆alkanoyl, N—C₂-C₆ alkanoylamino, N—C₁-C₆ alkylamino, N,N-di-C₁-C₆alkylamino, N—C₁-C₁₀ alkylcarbamoyl, N—C₁-C₁₀ alkylthiocarbamoyl,N,N-di-C₁-C₁₀ alkylcarbamoyl, N,N-di-C₁-C₁₀ alkylthiocarbamoyl, N—C₂-C₆alkenylcarbamoyl, N,N-di-C₂-C₆ alkenylcarbamoyl, N-amino C₁-C₁₀alkylcarbamoyl, N—C₁-C₆ alkoxy C₁-C₁₀ alkylcarbamoyl, N—C₁-C₆alkoxycarbonyl C₁-C₁₀ alkylcarbamoyl, N—C₁-C₆ alkoxycarbonylamino C₁-C₁₀alkylcarbamoyl, N—C₁-C₆ alkoxycarbonylamino C₁-C₆ alkoxycarbonyl, C₁-C₆alkylthio, C₁-C₆ alkylsulfinyl, C₁-C₆ alkylsulfonyl, N—C₁-C₆alkylsulfonylamino, C₁-C₆ alkoxy, C₁-C₆ alkoxycarbonyl, amino C₁-C₆alkoxycarbonyl, C₃-C₆ cycloalkylamino, N,N-di-C₃-C₆ cycloalkylamino,C₃-C₆ cycloalkyloxy, N—C₃-C₆ cycloalkylcarbamoyl and N,N-di-C₃-C₆cycloalkylcarbamoyl, (6) 5- or 6-membered heterocyclic groups selectedfrom the group consisting of the aforementioned series of groups A′, (7)monocyclic to tricyclic aromatic heterocyclic groups having per one ring1 to 5 hetero atoms selected from the group consisting of nitrogenatoms, oxygen atoms and sulfur atoms, selected from the group consistingof the aforementioned series of groups B′, (8) substituents selectedfrom the group consisting of N—C₁-C₁₀ alkylcarbamoyl groups, N—C₁-C₁₀alkylthiocarbamoyl groups, thiocarbonyl groups and carbonyl groups, eachsubstituted with the above-mentioned heterocyclic group or theabove-mentioned aromatic heterocyclic group, and (9) substituentsselected from the group consisting of straight-chain saturated C₁-C₉aliphatic groups, straight-chain unsaturated C₁-C₉ aliphatic groups,branched saturated C₁-C₉ aliphatic groups, branched unsaturated C₁-C₉aliphatic groups, C₁-C₆ alkoxy groups and C₁-C₆ alkylthio groups, eachof which groups may be substituted with the above-mentioned substituent,(hereinafter, the above-mentioned groups (5) to (9) are referred to asseries of groups C′), R^(1a) and R^(2a) are the same or different, andrepresent (1) groups selected from the group consisting of hydrogen,amino, carboxyl, cyano, sulfamoyl, sulfo, nitro, halogen, hydroxy,formyl, cyclic saturated C₃-C₉ aliphatic groups, cyclic unsaturatedC₃-C₉ aliphatic groups, aralkyl, aryl, N-arylamino, aryloxy, C₂-C₆alkanoyl, N—C₂-C₆ alkanoylamino, aroyl, N—C₁-C₆ alkylamino, N,N-di-C₁-C₆alkylamino, N—C₁-C₁₀ alkylcarbamoyl, N—C₁-C₆ alkylsulfamoyl, C₁-C₆alkylsulfinyl, C₁-C₆ alkylsulfonyl, N—C₁-C₆ alkylsulfonylamino, C₁-C₆alkoxy, C₁-C₆ alkoxycarbonyl, N—C₃-C₆ cycloalkylamino, C₃-C₆cycloalkyloxy and N—C₃-C₆ cycloalkylcarbamoyl; or (2) straight-chainsaturated C₁-C₉ aliphatic groups, straight-chain unsaturated C₁-C₉aliphatic groups, branched saturated C₁-C₉ aliphatic groups, branchedunsaturated C₁-C₉ aliphatic groups, or C₁-C₆ alkoxy groups, each ofwhich may optionally be substituted with the above-mentioned group,R^(3a) and R^(4a) are the same or different, and represent (1) groupsselected from the group consisting of hydrogen, azido, amidino, amino,carbamoyl, carbamoylamino, carbamoyloxy, carboxyl, guanidino, cyano,sulfamoyl, sulfo, nitro, halogen, hydroxy, formyl, formylamino, cyclicsaturated C₃-C₉ aliphatic groups, cyclic unsaturated C₃-C₉ aliphaticgroups, C₂-C₆ alkanoyl, N—C₁-C₆ alkylamino, N—C₁-C₁₀ alkylcarbamoyl,C₁-C₆ alkylthio, N—C₁-C₆ alkylsulfamoyl, C₁-C₆ alkylsulfinyl, C₁-C₆alkylsulfonyl, N—C₁-C₆ alkylsulfonylamino, C₁-C₆ alkoxy, C₁-C₆alkoxycarbonyl and N—C₃-C₆ cycloalkylamino, (2) groups selected from thegroup consisting of straight-chain saturated C₁-C₉ aliphatic groups,straight-chain unsaturated C₁-C₉ aliphatic groups, branched saturatedC₁-C₉ aliphatic groups and branched unsaturated C₁-C₉ aliphatic groups,each of which groups may optionally be substituted with theabove-mentioned group, or (3) (3-1) aryl groups, (3-2) monocyclic totricyclic C₇-C₁₅ aromatic carbocyclic groups selected from the groupconsisting of adamantyl, anthryl, indenyl, norbornyl and phenanthryl,(3-3) 5- or 6-membered heterocyclic groups selected from the groupconsisting of the aforementioned series of groups A′, (3-4) monocyclicto tricyclic aromatic heterocyclic groups having per one ring 1 to 5hetero atoms selected from the group consisting of nitrogen atoms,oxygen atoms and sulfur atoms, selected from the group consisting of theaforementioned series of groups B′,or (3-5) straight-chain saturatedC₁-C₉ aliphatic groups, straight-chain unsaturated C₁-C₉ aliphaticgroups, branched saturated C₁-C₉ aliphatic groups or branchedunsaturated C₁-C₉ aliphatic groups, each of which groups may optionallybe substituted with the above-mentioned aryl group, the above-mentionedaromatic carbocyclic group, the above-mentioned heterocyclic group orthe above-mentioned aromatic heterocyclic group, each of theabove-mentioned groups (3-1) to (3-5) being optionally substituted withone or more substituents selected from the group consisting of theaforementioned series of groups C′, or (4) R^(3a) and R^(4a) combinetogether to form a straight-chain saturated C₁-C₉ aliphatic group, astraight-chain unsaturated C₁-C₉ aliphatic group, a branched saturatedC₁-C₉ aliphatic group, a branched unsaturated C₁-C₉ aliphatic group, a5- or 6-membered saturated carbocyclic group, or a 5- or 6-memberedunsaturated carbocyclic group, X^(1a) represents an oxygen atom, asulfur atom or a group NR^(5a) (wherein R^(5a) represents a groupselected from the group consisting of hydrogen, halogen, hydroxy,N—C₁-C₆ alkylsulfonylamino, C₁-C₆ alkoxy, C₁-C₆ alkoxycarbonyl, C₂-C₆alkanoyl, carbamoyl and N—C₁-C₁₀ alkylcarbamoyl; or a straight-chainsaturated C₁-C₉ aliphatic group, a straight-chain unsaturated C₁-C₉aliphatic group, a branched saturated C₁-C₉ aliphatic group or abranched unsaturated C₁-C₉ aliphatic group, each of which groups mayoptionally be substituted with the above-mentioned group). X_(2a)represents an oxygen atom or a sulfur atom, Y_(a) represents an oxygenatom, a sulfur atom, a group NR^(5a) or a group CR^(6a)R^(7a) (whereinR^(6a) is a group selected from the group consisting of hydrogen,halogen. hydroxy, N—C₁-C₆ alkylsulfonylamino, C₁-C₆ alkoxy, C₁-C₆alkoxycarbonyl, C₂-C₆ alkanoyl, carbamoyl and N—C₁-C₁₀ alkylcarbamoyl:or a straight-chain saturated C₁-C₉ aliphatic group, a straight-chainunsaturated C₁-C₉ aliphatic group, a branched saturated C₁-C₉ aliphaticgroup or a branched unsaturated C₁-C₉ aliphatic group, each of whichgroups may optionally be substituted with the above-mentioned group,R^(7a) represents hydrogen or C₁-C₆ alkyl, and R^(5a) is as definedabove), and Z_(a) represents (1) a bi- or tricyclic saturated orunsaturated C₆-C₁₅ condensed carbocyclic group selected from the groupconsisting of condensed aryl, adamantyl, anthryl, indanyl, indenyl,C₆-C₈ cycloalkanyl, C₆-C₈ cycloalkadienyl, C₆-C₈ cycloalkenyl, norbornyland phenanthryl, (2) a 6-membered heterocyclic group selected from thegroup consisting of ethylenedioxyphenyl, pyridyl, pyrazinyl,pyrimidinyl, pyridazinyl, benzimidazolyl, benzoxazolyl, benzothiazolyl,benzotriazolyl, benzofuranyl and methylenedioxyphenyl, or (3) a bi- ortricyclic condensed aromatic heterocyclic group having per one ring 1 to5 hetero atoms selected from the group consisting of nitrogen atoms,oxygen atoms and sulfur atoms.
 3. The compound represented by thegeneral formula [I-b] or pharmaceutically acceptable salt thereof,according to claim 1 or 2;

wherein, R^(b) represents (1) an aryl group; (2) a mono- to tricyclicC₇-C₁₅ aromatic carbocyclic group selected from the group consisting ofanthryl and phenanthryl; (3) a 5- or 6-membered heterocyclic groupselected from the group consisting of thienyl, pyridyl, pyrazinyl,pyrimidinyl, furyl, tetrahydrofuranyl and morpholino; or (4) a mono- totricyclic aromatic heterocyclic group having per one ring 1 to 5 heteroatoms selected from the group consisting of nitrogen atoms, oxygen atomsand sulfur atoms, selected from the group consisting ofethylenedioxyphenyl, dibenzofuranyl, dibenzothiophenyl andmethylenedioxyphenyl, each of the above-mentioned groups (1) to (4)being optionally substituted with one or more substituents selected fromthe group consisting of (5) substituents selected from the groupconsisting of amino, carbamoyl, carboxyl, nitro, halogen, hydroxy,aralkylcarbonyl, N-aralkylcarbamoyl, aryl, aroyl, C₂-C₆ alkanoyl,N—C₁-C₆ alkylamino, N—C₁-C₁₀ alkylcarbamoyl, N—C₁-C₁₀alkylthiocarbamoyl, N,N-di-C₁-C₁₀ alkylcarbamoyl, N,N-di-C₁-C₁₀alkylthiocarbamoyl, N—C₂-C₆ alkenylcarbamoyl, N,N-di-C₂-C₆alkenylcarbamoyl, N-amino C₁-C₁₀ alkylcarbamoyl, N—C₁-C₆ alkoxy C₁-C₁₀alkylcarbamoyl, N—C₁-C₆ alkoxycarbonyl C₁-C₁₀ alkylcarbamoyl, C₁-C₆alkoxy, amino C₁-C₆ alkoxycarbonyl, N—C₃-C₆ cycloalkylamino,N,N-di-C₃-C₆ cycloalkylamino, C₃-C₆ cycloalkyloxy, N—C₃-C₆cycloalkylcarbamoyl and N,N-di-C₃-C₆ cycloalkylcarbamoyl, (6) 5- or6-membered heterocyclic groups selected from the group consisting ofthienyl, pyridyl, pyrazinyl, pyrimidinyl, furyl, tetrahydrofuranyl andmorpholino, (7) monocyclic to tricyclic aromatic heterocyclic groupshaving per one ring 1 to 5 hetero atoms selected from the groupconsisting of nitrogen atoms, oxygen atoms and sulfur atoms, selectedfrom the group consisting of ethylenedioxyphenyl, dibenzofuranyl,dibenzothiophenyl and methylenedioxyphenyl, (8) substituents selectedfrom the group consisting of N—C₁-C₁₀ alkylcarbamoyl groups, N—C₁-C₁₀alkylthiocarbamoyl groups, thiocarbonyl groups and carbonyl groups, eachsubstituted with the above-mentioned heterocyclic group or theabove-mentioned aromatic heterocyclic group, and (9) substituentsselected from the group consisting of straight-chain saturated C₁-C₉aliphatic groups, straight-chain unsaturated C₁-C₉ aliphatic groups,branched saturated C₁-C₉ aliphatic groups, branched unsaturated C₁-C₉aliphatic groups and C₁-C₆ alkoxy groups, each of which groups may besubstituted with the above-mentioned substituent, (hereinafter, theabove-mentioned groups (5) to (9) are referred to as series of groupsC″) R^(1b) and R^(2b) are the same or different, and represent (1)groups selected from the group consisting of hydrogen, amino, nitro,halogen, hydroxy, aryl, N-arylamino, N—C₁-C₆ alkylamino, N,N-di-C₁-C₆alkylamino, N—C₁-C₁₀ alkylcarbamoyl, C₁-C₆ alkoxy, C₁-C₆ alkoxycarbonyland N—C₃-C₆ cycloalkylamino, or (2) straight-chain saturated C₁-C₉aliphatic groups, straight-chain unsaturated C₁-C₉ aliphatic groups,branched saturated C₁-C₉ aliphatic groups, branched unsaturated C₁-C₉aliphatic groups, or C₁-C₆ alkoxy groups, each of which may optionallybe substituted with the above-mentioned group, R^(3b) and R^(4b) are thesame or different, and represent (1) groups selected from the groupconsisting of hydrogen, azido, amidino, amino, carbamoyl, carboxyl,guanidino, cyano, sulfamoyl, sulfo, nitro, halogen, hydroxy, formyl,cyclic saturated C₃-C₉ aliphatic groups, cyclic unsaturated C₃-C₉aliphatic groups, N—C₁-C₆ alkylamino, N—C₁-C₁₀ alkylcarbamoyl, C₁-C₆alkylthio, C₁-C₆ alkoxy and C₁-C₆ alkoxycarbonyl, (2) groups selectedfrom the group consisting of straight-chain saturated C₁-C₉ aliphaticgroups, straight-chain unsaturated C₁-C₉ aliphatic groups, branchedsaturated C₁-C₉ aliphatic groups and branched unsaturated C₁-C₉aliphatic groups, each of which groups may optionally be substitutedwith the above-mentioned group, or (3) (3-1) aryl groups, (3-2)monocyclic to tricyclic C₇-C₁₅ aromatic carbocyclic groups selected fromthe group consisting of anthryl and phenanthryl, (3-3) 5- or 6-memberedheterocyclic groups selected from the group consisting of thienyl,pyridyl, pyrazinyl, pyrimidinyl, furyl, tetrahydrofuranyl andmorpholino, (3-4) monocyclic to tricyclic aromatic heterocyclic groupshaving per one ring 1 to 5 hetero atoms selected from the groupconsisting of nitrogen atoms, oxygen atoms and sulfur atoms, selectedfrom the group consisting of ethylenedioxyphenyl, dibenzofuranyl,dibenzothiophenyl and methylenedioxyphenyl, or (3-5) straight-chainsaturated C₁-C₉ aliphatic groups, straight-chain unsaturated C₁-C₉aliphatic groups, branched saturated C₁-C₉ aliphatic groups or branchedunsaturated C₁-C₉ aliphatic groups, each of which groups may optionallybe substituted with the above-mentioned aryl group, the above-mentionedaromatic carbocyclic group, the above-mentioned heterocyclic group orthe above-mentioned aromatic heterocyclic group, each of theabove-mentioned groups (3-1) to (3-5) being optionally substituted withone or more substituents selected from the group consisting of theaforementioned series of groups C″, or (4) R^(3b) and R^(4b) combinetogether to form a straight-chain unsaturated C₁-C₉ aliphatic group or a5- or 6-membered saturated carbocyclic group, X_(1b) represents anoxygen atom or a group NR^(5b) (wherein R^(5b) represents a groupselected from the group consisting of hydrogen, hydroxy, C₁-C₆ alkoxy,C₁-C₆ alkoxycarbonyl and N—C₁-C₁₀ alkylcarbamoyl; or a straight-chainsaturated C₁-C₉ aliphatic group, a straight-chain unsaturated C₁-C₉aliphatic group, a branched saturated C₁-C₉ aliphatic group or abranched unsaturated C₁-C₉ aliphatic group, each of which groups mayoptionally be substituted with the above-mentioned group), X_(2b)represents an oxygen atom or a sulfur atom, Y_(b) represents an oxygenatom, a sulfur atom or a group CR^(6b)R^(7b) (wherein R^(6b) is a groupselected from the group consisting of hydrogen, hydroxy, C₁-C₆ alkoxy,C₁-C₆ alkoxycarbonyl and N—C₁-C₁₀ alkylcarbamoyl; or a straight-chainsaturated C₁-C₉ aliphatic group, a straight-chain unsaturated C₁-C₉aliphatic group, a branched saturated C₁-C₉ aliphatic group or abranched unsaturated C₁-C₉ aliphatic group, each of which groups may besubstituted with the above-mentioned group, and R^(7b) representshydrogen or C 1-C₆ alkyl), and Z_(b) represents (1) a bi- or tricyclicsaturated or unsaturated C₆-C₁₅ condensed carbocyclic group selectedfrom the group consisting of condensed aryl, anthryl, C₆-C₈cycloalkanyl, C₆-C₈ cycloalkadienyl and C₆-C₈ cycloalkenyl, (2) a6-membered heterocyclic group selected from the group consisting ofethylenedioxyphenyl, pyridyl, pyrazinyl, pyrimidinyl, pyridazinyl andmethylenedioxyphenyl, or (3) a bi- or tricyclic condensed aromaticheterocyclic group having per one ring 1 to 5 hetero atoms selected fromthe group consisting of nitrogen atoms, oxygen atoms and sulfur atoms.4. The compound represented by the general formula [I-c] orpharmaceutically acceptable salt thereof, according to claim 1;

wherein, R^(c) represents an aryl group, a mono- to tricyclic C₇-C₁₅aromatic carbocyclic group (excluding an aryl group), a 5- or 6-memberedheterocyclic group, or a mono- to tricyclic aromatic heterocyclic grouphaving per one ring 1 to 5 hetero atoms selected from the groupconsisting of nitrogen atoms, oxygen atoms and sulfur atoms (excluding a5- or 6-membered heterocyclic group), R^(1c) and R^(2c) are the same ordifferent, and represent (1) groups selected from the group consistingof hydrogen, azido, amino, carbamoyl, carbamoylamino, carbamoyloxy,carboxyl, cyano, sulfamoyl, sulfo, nitro, halogen, hydroxy, formyl,formylamino, cyclic saturated or unsaturated C₃-C₉ aliphatic groups,aralkyl, N-aralkylamino, aralkyloxy, aralkylcarbonyl, aryl, N-arylamino,aryloxy, arylsulfonyl, N-arylsulfonylamino, N-arylsulfonylamino C₁-C₆alkylamino, N-arylsulfonylamino C₁-C₁₀ alkylcarbamoyl, arylsulfonylaminoC₁-C₆ alkoxycarbonyl, C₂-C₆ alkanoyl, N—C₂-C₆ alkanoylamino, aroyl,N-aroylamino, N-aroyl C₁-C₆ alkylamino, N-aroyl C₁-C₁₀ alkylcarbamoyl,N—C₁-C₆ alkylamino, N,N-di-C₁-C₆ alkylamino, N—C₁-C₁₀ alkylcarbamoyl,N,N-di-C₁-C₁₀ alkylcarbamoyl, N—C₁-C₆ alkylsulfamoyl, C₁-C₆alkylsulfinyl, C₁-C₆ alkylsulfonyl, C₁-C₆ alkylthio, C₁-C₆ alkoxy, C₁-C₆alkoxycarbonyl, N—C₃-C₆ cycloalkylamino, C₃-C₆cycloalkyloxy and N-C₃-C₆cycloalkylcarbamoyl, or (2) straight-chain or branched and saturated orunsaturated C₁-C₉ aliphatic groups, N-C₁-C₆ alkylamino groups, C₁-C₆alkylthio groups, or C₁-C₆ alkoxy groups, each of which groups mayoptionally be substituted with the above group, R^(3c) and R^(4c) arethe same or different, and represent (1) groups selected from the groupconsisting of hydrogen, azido, amidino, amino, carbamoyl,carbamoylamino, carbamoyloxy, carboxyl, guanidino, cyano, sulfamoyl,sulfo, nitro, halogen, hydroxy, formyl, formylamino, cyclic saturatedC₃-C₉ aliphatic groups, cyclic unsaturated C₃-C₉ aliphatic groups, C₂-C₆alkanoyl, N—C₂-C₆ alkanoylamino, N—C₁-C₆ alkylamino, N,N-di-C₁-C₆alkylamino, N—C₁-C₁₀ alkylcarbamoyl, N,N-di-C₁-C₁₀ alkylcarbamoyl, C₁-C₆alkylthio, N—C₁-C₆ alkylsulfamoyl, C₁-C₆ alkylsulfinyl, C₁-C₆alkylsulfonyl, C₁-C₆ alkoxy, C₁-C₆ alkoxycarbonyl, N—C₃-C₆cycloalkylamino, C₃-C₆ cycloalkyloxy and N—C₃-C₆ cycloalkylcarbamoyl,(2) straight-chain or branched and saturated or unsaturated C₁-C₉aliphatic groups optionally substituted with the above-mentioned group,(3) (3-1 ) aryl groups, (3-2) monocyclic to tricyclic C₇-C₁₅ aromaticcarbocyclic groups (excluding aryl groups), (3-3) 5- or 6-memberedheterocyclic groups, (3-4) monocyclic to tricyclic aromatic heterocyclicgroups having per one ring 1 to 5 hetero atoms selected from the groupconsisting of nitrogen atoms, oxygen atoms and sulfur atoms (excluding5- or 6-membered heterocyclic groups), or (3-5) straight-chain orbranched and saturated or unsaturated C₁-C₉ aliphatic groups optionallysubstituted with the above-mentioned aryl group, aromatic carbocyclicgroup, heterocyclic group or aromatic heterocyclic group, each of thegroups (3-1) to (3-5) being optionally substituted with substituent(s),or (4) R³c and R⁴c combine together to form a straight-chain or branchedunsaturated C₁-C₉ aliphatic group, or a 5- or 6-membered saturated orunsaturated carbocyclic group, X_(1c) and X_(2c) are the same ordifferent, and represent oxygen atoms or sulfur atoms, Y_(c) representsan oxygen atom, a sulfur atom, a group CHR^(5c) or a group NR^(5c)(wherein R^(5c) represents a group selected from the group consisting ofhydrogen, halogen, hydroxy, C₁-C₆ alkoxy, C₂-C₆ alkanoyl, carbamoyl andN—C₁-C₁₀ alkylcarbamoyl; or a straight-chain or branched and saturatedor unsaturated C₁-C₉ aliphatic group optionally substituted with theabove-mentioned group), and Z_(c) represents a condensed aryl group; abi- or tricyclic saturated or unsaturated C₆-C₁₅ condensed carbocyclicgroup (excluding a condensed aryl group); a 6-membered heterocyclicgroup; or a bi- or tricyclic condensed aromatic heterocyclic grouphaving per one ring 1 to 5 hetero atoms selected from the groupconsisting of nitrogen atoms, oxygen atoms and sulfur atoms (excluding a6-membered heterocyclic group).
 5. A process for preparing a compoundrepresented by the general formula [I′]

wherein, Y₁ represents an oxygen atom, a group NR⁵ or a group CR⁶R⁷(wherein, R⁵, R⁶ and R⁷ are as defined above, and R, R¹, R², R³, R⁴, X₁,X₂ and Z are as defined above, or a pharmaceutically acceptable saltthereof, which comprises reacting a carboxylic acid or thiocarboxylicacid represented by the general formula [II]

wherein, R⁰ represents (1) an aryl group, (2) a mono- to tricyclicC₇-C₁₅ aromatic carbocyclic group selected from the group consisting ofacenaphthylenyl, adamantyl, anthryl, indenyl, norbornyl and phenanthryl,(3) a 5- or 6-membered heterocyclic group selected from the groupconsisting of the aforementioned series of groups A, or (4) a mono- totricyclic aromatic heterocyclic group having per one ring 1 to 5 heteroatoms selected from the group consisting of nitrogen atoms, oxygen atomsand sulfur atoms, selected from the group consisting of theaforementioned series of groups B, each of the above-mentioned groups(1) to (4) being optionally substituted with one or more substituentsselected from the group consisting of the aforementioned series ofgroups C provided that amino, carboxyl, hydroxyl, N-amino C₁-C₁₀alkylcarbamoyl and amino C₁-C₆ alkoxycarbonyl may optionally beprotected, R¹⁰ and R²⁰ are the same or different, and represent (1)groups selected from the group consisting of the aforementioned seriesof groups D provided that amino, carboxyl and hydroxyl may optionally beprotected, or (2) straight-chain saturated C₁-C₉ aliphatic groups,straight-chain unsaturated C₁-C₉ aliphatic groups, branched saturatedC₁-C₉ aliphatic groups, branched unsaturated C₁-C₉ aliphatic groups,N—C₁-C₆ alkylamino groups, C₁-C₆ alkylthio groups, or C₁-C₆ alkoxygroups, each of which groups may optionally be substituted with theabove-mentioned group, and X₂ and Z are as defined above, with an aminederivative represented by the general formula [III]

wherein, Y₁₀ represents an oxygen atom, a group NR⁵⁰ or a group CR⁶⁰R⁷(wherein R⁵⁰ represents a group selected from the group consisting ofhydrogen, a protective group for amino groups, halogen, optionallyprotected hydroxy, N—C₁-C₆ alkylsulfonylamino, C₁-C₆ alkoxy, C₁-C₆alkoxycarbonyl, C₂-C₆ alkanoyl, carbamoyl and N—C₁-C₁₀ alkylcarbamoyl;or a straight-chain saturated C₁-C₉ aliphatic group, a straight-chainunsaturated C₁-C₉ aliphatic group, a branched saturated C₁-C₉ aliphaticgroup or a branched unsaturated C₁-C₉ aliphatic group, each of whichgroups may optionally be substituted with the above-mentioned group, R⁶⁰represents a group selected from the group consisting of hydrogen,halogen, optionally protected hydroxy, N—C₁-C₆ alkylsulfonylamino, C₁-C₆alkoxy, C₁-C₆ alkoxycarbonyl, C₂-C₆ alkanoyl, carbamoyl and N—C₁-C₁₀alkylcarbamoyl; or a straight-chain saturated C₁-C₉ aliphatic group, astraight-chain unsaturated C₁-C₉ aliphatic group, a branched saturatedC₁-C₉ aliphatic group or a branched unsaturated C₁-C₉ aliphatic group,each of which groups may optionally be substituted with theabove-mentioned group, and R⁷ is as defined above), R³⁰ and R⁴⁰ are thesame or different, and represent (1) groups selected from the groupconsisting of the aforementioned series of groups E provided that amino,carboxyl and hydroxyl may optionally be protected, (2) groups selectedfrom the group consisting of straight-chain saturated C₁-C₉ aliphaticgroups, straight-chain unsaturated C₁-C₉ aliphatic groups, branchedsaturated C₁-C₉ aliphatic groups and branched unsaturated C₁-C₉aliphatic groups, each of which groups may optionally be substitutedwith the above-mentioned group, or (3) (3-1) aryl groups, (3-2)monocyclic to tricyclic C₇-C₁₅ aromatic carbocyclic groups selected fromthe group consisting of acenaphthylenyl, adamantyl, anthryl, indenyl,norbornyl and phenanthryl, (3-3) 5- or 6-membered heterocyclic groupsselected from the group consisting of the aforementioned series ofgroups A, (3-4) monocyclic to tricyclic aromatic heterocyclic groupshaving per one ring 1 to 5 hetero atoms selected from the groupconsisting of nitrogen atoms, oxygen atoms and sulfur atoms, selectedfrom the group consisting of the aforementioned series of groups B, or(3-5) straight-chain saturated C₁-C₉ aliphatic groups, straight-chainunsaturated C₁-C₉ aliphatic groups, branched saturated C₁-C₉ aliphaticgroups or branched unsaturated C₁-C₉ aliphatic groups, each of whichgroups may optionally be substituted with the above-mentioned arylgroup, the above-mentioned aromatic carbocyclic group, theabove-mentioned heterocyclic group or the above-mentioned aromaticheterocyclic group, each of the above-mentioned groups (3-1) to (3-5)being optionally substituted with one or more substituents selected fromthe group consisting of the aforementioned series of groups C providedthat amino, carboxyl, hydroxyl, N-amino C₁-C₁₀ alkylcarbamoyl and aminoC₁-C₆ alkoxycarbonyl may optionally be protected, or (4) R³⁰ and R⁴⁰combine together to form a straight-chain saturated C₁-C₉ aliphaticgroup, a straight-chain unsaturated C₁-C₉ aliphatic group, a branchedsaturated C₁-C₉ aliphatic group, a branched unsaturated C₁-C₉ aliphaticgroup, a 5- or 6-membered saturated carbocyclic group, or a 5- or6-membered unsaturated carbocyclic group, L₁ represents a hydrogen atom,a protective group for carboxyl groups, a protective group for aminogroups, or a resin carrier of carboxyl groups or amino groups in solidsynthesis of peptides, and X₁₀ represents an oxygen atom, a sulfur atomor a group NR⁵⁰ (wherein R⁵⁰ is as defined above), and removing theprotective group for amino groups, the protective group for hydroxylgroups or the protective group for carboxyl groups, according tonecessity, to form an equilibrium mixture of a compound represented bythe general formula [IV′]

wherein, R⁰, R¹⁰, R²⁰, R³⁰, R⁴⁰, L₁, X₂, X₁₀, Y₁ and Z are as definedabove, and a compound represented by the general formula [V′]

wherein, R⁰, R¹⁰, R²⁰, R³⁰, R⁴⁰, L₁, X₂, X₁₀, Y₁ and Z are as definedabove, and then reacting the equilibrium mixture with an acid in aninert organic solvent to form a compound represented by the generalformula [VIII′]

wherein, R⁰, R¹⁰, R²⁰, R³⁰, R⁴⁰, X₂, X₁₀, Y₁ and Z are as defined above,and removing the protective groups, when exist.
 6. A process forpreparing a compound represented by the general formula [I″]

wherein, Y₃ represents a sulfur atom, and R, R¹, R², R³, R⁴, X₁, X₂ andZ are as defined above, or a pharmaceutically acceptable salt thereof,which comprises reacting an equilibrium mixture of a compoundrepresented by the general formula [IV″]

wherein, Y₂ represents an oxygen atom, L₂ represents a hydrogen atom,and R⁰, R¹⁰, R²⁰, R³⁰, R⁴⁰, X₂, X₁₀ and Z are as defined above, and acompound represented by the general formula [V″]

wherein, R⁰, R¹⁰, R²⁰, R³⁰, R⁴⁰, L₂, X₂, X₁₀, Y₂ and Z are as definedabove, with a sulfurizing agent to form an equilibrium mixture of acompound represented by the general formula [VI″]

wherein, R⁰, R¹⁰, R²⁰, R³⁰, R⁴⁰, L₂, X₂, X₁₀, Y₃ and Z are as definedabove, and a compound represented by the general formula [VII″]

wherein, R⁰,R¹⁰, R²⁰, R³⁰, R⁴⁰, L₂, X₂, X₁₀, Y₃ and Z are as definedabove, and then reacting the formed equilibrium mixture with an acid toform a compound represented by the general formula [VIII″]

wherein, R⁰, R¹⁰, R²⁰, R³⁰, R⁴⁰, X₂, X₁₀, Y₃ and Z are as defined above,and removing the protective groups, when exist.
 7. An agent for treatingdiabetes, a prophylactic agent for chronic complications of diabetes ora drug against obesity, containing, as an effective ingredient, acompound represented by the general formula [I]

wherein, R, R¹, R², R³, R⁴, X₁, X₂, Y and Z are as defined above, or apharmaceutically acceptable salt thereof.